About Leukemia

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About Leukemia Biography

Leukemia is a cancer of the bone marrow and blood. There are four main types of leukemia. These are: acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), acute myelogenous leukemia (AML), and chronic myelogenous leukemia (CML). MLL stands for “mixed lineage leukemia” and means that the leukemia comes from both the myeloid and the lymphoid cell progenitors (Robien and Ulrich, 2003). The cause of leukemia is currently still unknown. It often arises as a result of DNA translocations, inversions, or deletions in genes regulating blood cell development or homeostasis. In all types of leukemia, genetic translocations, inversions, or deletions cause dysfunctional cells to replace normal hematopoietic cells in the bone marrow (Robien and Ulrich, 2003). A leukemia patient will usually die from anemia or infection because of the lack of red blood cells and immune cells (Sompayrac, 1999).

Leukemia stem cells (LSC) are thought to have been derived from haematopoietic stem cells (HSC), which are CD34+CD38-. During leukemogenesis, the LSC expresses shared surface characteristics with the HSC. It also has the capacity for producing both the clonogenic leukemic progenitors and the non-clonogenic blast cells, which make up the bulk of the leukemia (Huntly, et al. 2005). In the bone marrow there are two types of hematopoietic stem cells. In someone who does not have leukemia, the myeloid progenitor is the parent cell to granulocytes and macrophages, and the lymphoid progenitor is the parent cell to T-cells and B-cells (Janeway, et al., 1999). In adults, 85% of all leukemia cases are myeloid, with 15% being lymphoid. In children the opposite is true, with 80% of all cases being lymphoid (ALL) and only 20% being myeloid (Greaves, 2000).

In people with acute leukemia, a mistake is made in the action of the VDJ recombinase enzyme, which normally creates antibody and T-cell receptor diversity. Proto-oncogene, a gene that promotes growth and spread, is inappropriately turned on and it activates other proto-oncogenes and deactivate anti-oncogenes, which normally protect cells against cancer-causing mutations (Sompayrac, 1999). Chronic leukemias may be caused when mistakes in recombination activate genes that either cause the cell to proliferate, or cause it not to die by apoptosis or increased activity of stem cells or abnormal committed progenitor cells (Marley and Gordon, 2005). The increased life span of the cell increases the chance that enough mutations will accumulate to cause cancer (Sompayrac, 1999).

Mutations that increase the risk of leukemia can be caused by radiation, extremely low frequency electromagnetic fields, pesticides, benzene, other carcinogens, viral infections, and recombination errors that occur throughout life (Sompayrac, 1999). Cigarette smoke, high altitude, or other factors that increase exposure to radiation can be accelerating factors for cancer (Sompayrac, 1999). Rates of leukemia may also be greater following periods of population mixing. During periods of population mixing, individuals are exposed to new infectious agents. A similar hypothesis is that children who were not exposed to common infectious agents at a young age would also have higher rates of leukemia. The infectious agents would be new to their system, causing a strong and inappropriate immune response that might trigger leukemia. Studies on daycare attendance as a measure of exposure to infectious agents have had mixed results (Robien and Ulrich, 2003).

Immuno-suppressed people such as patients being treated with chemotherapy or patients who have AIDS have higher rates of leukemia, but they do not have higher rates of other types of cancer (Sompayrac, 1999). Some cells in the immune system may protect against the development of cancer. Macrophages are cells that eat and destroy old or damaged red blood cells. The macrophages recognize the cells because a fat molecule called phospotidyl-serine flips to the outside of the cell as it ages (Sompayrac, 1999). Macrophages can also destroy cancer cells, but only when they are hyperactivated. Usually when there is no inflammatory reaction in the body, the macrophages will remain resting and will not attack the cancer cells, but natural killer cells secrete cytokines when cancer cells are present and the cytokines cause the hyperactivation of the macrophages (Sompayrac, 1999). The immune system has evolved to protect against leukemia by destroying cancerous cells, but in a person whose immune system is weakened or is being exposed to many new pathogens, it is not as effective at getting rid of damaged cells.

Specific Types of Leukemia
ALL is a disease of B or T lymphocyte lineage. Childhood ALL is of the B lineage. One of the most common translocations in B-precursor childhood ALL is suggested to be t(1;19)(q23;p13). The deletion of 9p has been suggested to be an evolutionary aspect of the progression of ALL but it is also thought to play a primary role in some cases of leukemogenesis (Forestier, et al., 2000). In ALL, it seems likely that leukemia develops in two stages: a pre-natal genetic alteration that predisposes the infant to developing leukemic precursor cells, and a post-natal event that triggers this latent disease. This has been suggested by several studies, including a number of "twin studies," which compare the incidence of diseases in identical (monozygotic) and fraternal (dizygotic) twins, in order to determine the relative importance of genetics and the environment as causal factors in a specific disease. Many twin studies have shown that identical twins have high "concordance" levels for leukemia, meaning that they share the disease. Concordance has often been taken as proof that a disease is genetic. However, in this case, it may be because they share a very similar environment during their fetal development: more than half of identical twins share a placenta, while no fraternal twins do (Greaves, 1999). The leukemic genetic alteration most likely takes place in one twin and spreads to the other through the placenta. This suggests that in non-twin children, the leukemic alteration may also take place in utero, as indicated by positive results from blood samples taken soon after birth (Greaves, 1999). Concordance rates near 100% would imply that the initial leukemic genetic alteration is the sole and sufficient cause for the development of leukemia. This is the case with another type of leukemia, MLL. However, in ALL, the concordance rate is closer to 10%. This suggests that the initial genetic alteration is not enough to cause leukemia in the absence of a second genetic alteration caused by the post-natal environment (Greaves, et al, 2003).

CML is caused by the reproduction of cells that have not matured properly, but continue to reproduce (Marley and Gordon, 2005). It has a distinguishing inherited characteristic called the Philadelphia chromosome (No. 22), a genetic abnormality in the blood cells that is referred to as the Ph-chromosome.  The breakage on the chromosome is referred to as "BCR" (breakpoint cluster region). A breakage on chromosome 9, known as "ABL" (Abelson) has also been noted. These two mutated genes fuse together, forming a gene called BCR-ABL.  This gene can still function properly. However, in CML patients, the protein that is produced is abnormal, causing unregulated myeloid cell production. Evidence has pointed to this abnormal protein production as the cause of the leukemic conversion of the hematopoietic stem cell (Leukemia and Lymphoma Society, 2005). Normally stem cells divide in the bone marrow to replace themselves and create differentiating cells. In CML, either the stem cells or progenitor cells are increasing at all times (Marley and Gordon, 2005).

The most common genetic abnormality in CLL is 13q14 deletion, observed in 50% of all cases. (Caporaso et al., 2004)

In addition to the four basic types of leukemia, there are a variety of other forms. Different types of leukemia are characterized by different patterns of nonrandom chromosomal aberrations, but the frequencies with which the various karyotypic subtypes are seen differ amongst geographic regions. In areas where children are not sufficiently exposed in early youth to childhood infections, there is a greater risk of developing leukemia from an abnormal immune system response.

What Is Leukemia

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What Is Leukemia Biography

Maya Scholars, in Mexico, Guatemala, Belize, Honduras, El Salvador and North America, have been watching with amusement and dismay as self-styled experts proclaim that ancient Maya prophets foretold an earth-shattering happening to occur December 21, 2012. This predicted phenomenon gets described in contradictory but often cataclysmic fashion--as an ecological collapse, a sunspot storm, a rare cosmic conjunction of the earth, sun, and the galactic center, a new and awesome stage of our evolution, and even a sudden reversal of the Earth's magnetic field which will erase all our computer drives. One even predicts the earth's initiation into a Galactic Federation, whose elders have been accelerating our evolution with a "galactic beam" for the last 5000 years. In sum, the world as we know it will suddenly come to a screeching halt.

These predictions are alleged to be prophecies by so-called "Ancient Mayans" whose "astronomically precise" calendar supposedly terminates on that date. According to such accounts, these mysterious Maya geniuses appeared suddenly, built an extraordinary civilization, designed in it clues for us, and then suddenly, inexplicably, vanished, as if they had completed their terrestrial mission. These same experts claim special credibility for the Maya prophecies by asserting that these historic sages, with their possible extraterrestrial origins, had tapped into an astonishing esoteric wisdom.

Could any of this be true?
The credibility of those claims deserves rational attention-which is what I intend to provide. Neither mystic nor prophet, I am a Mayanist. More specifically, I am a professional art historian and an epigrapher (less formally, a glypher), one who can read and write Maya hieroglyphs. For over a decade, I have focused my scholarly research specifically on Maya culture and writing, making some surprising discoveries that can present a more definitive perspective on the prophecies of the ancient Maya seers. As we approach the critical year, it is time to offer a more viable account of the Maya prophecy and expose both the fallacies and ethnocentricism tainting the current sensational accounts.

Here I intend to explain what we actually know about (1) Maya knowledge and attitudes, both ancient and modern, (2) the date 13.0.0.0.0. and (3) their many Creation stories and prophecies. I shall draw from recent decipherment, ethnography, interviews with Maya priests and knowledge-keepers, and especially from their surviving prophetic literature. That literature includes The Books of Chilam Balam, among others, the pre-Columbian Codices, and ancient inscriptions. The evidence is sometimes fragmentary and often puzzling to us moderns, at least at first. But I believe the effort will be worth it.

First, let me affirm that the year 2012 does hold particular significance in Mayan scholarship. Those of us who study the ancient and modern Maya — anthropologists, archaeologists, art historians, linguists, historians, amateurs, collectors — have been anticipating the end of the Maya Great Cycle for some time. We write it 13.0.0.0.0 4 Ajaw 3 K'ank'in. We have known for half a century that this date probably correlates to December 21 (or December 23) in the year 2012 in the Gregorian calendar.

Leukemia

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Leukemia Biography

Leukemia, a malignant cancer of the blood, was named in 1847 by Dr. Rudolf Virchow, a German politician whose wide-ranging interests led him to significant discoveries in cell biology, pathology and anthropology. Although Dr. Virchow’s name appeared often in The New York Times, mostly in the late 19th century, his discovery of leukemia was not mentioned until Feb. 22, 1970, in an article by Dr. Lawrence K. Altman.
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Of course, that was not the first time the disease was mentioned in the paper. That happened on Dec. 6, 1899, when Maj. Samuel T. Armstrong, surgeon of the 32nd Infantry, died in Manila. “The cause of death,” the brief obituary said, “is given as leukemia.”

By 1913, several types of leukemia were known, although none were treatable. On Dec. 2 of that year, The Times mentioned the illness in a report on the death of a Cornell student “suffering from a grave blood disease described by the hospital authorities as acute lymphatic leukemia.” This was also the first mention of an attempt to treat the disease — with a blood transfusion from the patient’s twin brother.

The next failed treatment noted in the paper was radium. On May 3, 1915, The Times reported that radium “has also been found effective in leukemia,” but then acknowledged that “patients might even succumb to the poisons released into the system.” Still, this was the first mention of a treatment, radiation therapy, that today remains one of the treatments for the illness.

The disease began to get significant public recognition only in the late 1920s. On March 5, 1927, The Times reported that a “Dutch gentleman” had offered an award of 25,000 guilders “for the most satisfactory treatise on the treatment of leukemia.” On April 3, 1934, in an article about a dying 4-year-old girl, a reporter described the disease as “an overabundance of white corpuscles in the blood,” adding that “its cure is infrequent.”

Throughout the 1930s, leukemia was frequently mentioned as a cause of illness and almost inevitable death, often in connection with heroic blood donations and transfusions in ultimately futile attempts to cure it. The disease, discovered almost a century before, had now become part of the public discourse.

The first suggestion to readers of The Times that a chemical approach might work was on April 13, 1946, when an anonymous reporter noted that because some of the chemicals tested and rejected for malaria treatment “destroy white blood cells, they may yet have their uses in leukemia.”

Today, more than 100 years after the first mention of the disease in The Times, treatment is complex, involving the skills of many specialists — hematologists, medical and radiation oncologists, pediatric leukemia specialists, nurses and dietitians. The many types of leukemia can be successfully treated, and sometimes cured, with chemotherapy, stem cell transplants and biological therapies that enhance the body’s immune system.

A Lymphoma

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A Lymphoma Biography
I started a new treatment in March, a week late, as I had to help move my grandma, since only one of her 6 children (plus 5 spouses) would help. My bf was going to help, but she changed the moving date, and he had already booked a day off for moving her.
So my mother and I were the only ones there to move her.

In April, I woke up with a swollen face, for no particular reason. Or at least, no reason was found.

I got a hickman line for my treatment, because my veins are so small, etc. I feel sorry for the nurses who have to find my veins. I have freaked a few out, causing them to poke and search numerous times for ONE IV insertion.

In May, the line got infected… I took a road trip to Wichita, Kansas from Buffalo, NY. 20 hour drive! With the stops for food, gas, rest, etc. it took 24 hours. I was very excited that my time estimation was right on! And I over estimated the fuel costs, so we had a good trip overall.

I woke up again beginning of June, with a swollen face. This time it was more intense, and went down to my throat. It was so bad that it altered my voice! I went to the local urgent care, and got a shot of Benedryl and a steroid shot. One in each buttock! OUCH!
I ended up in hospital for a week in June, for an undetermined infection. That was “fun”! It was during the 2nd week of my daughter’s summer visit. But I called her everyday, a few times a day. My friend was also going through a rough time, due to domestic abuse.

My hickman line was removed in July. That took a while to heal, due to the infection.

August was pretty uneventful, thankfully. August was also the end of my treatment.

First weekend of September, I spiked a fever of 105! Again I was admitted to hospital for a week. The doctor I had that time was insane, inconsiderate and useless. She did some of the stupidest things. Didn’t give me blood until 3 days after being there, when I went in with a low hemoglobin, and it dropped further the next day. Then she gave me something after the blood to help flush the excess fluids… this was at MIDNIGHT! The next day I had to take medical transport 2 hours away to go see my oncologist, so due to the medication she gave me to flush the fluids, we had to stop, so we were late. Didn’t help that the transport arrived to pick me up late, AND we had to stop for GAS! Crazy people!

October was somewhat crazy, because I was moving, and no one showed up to help, so it took my bf and I 2 weeks to move our stuff across the street. We were supposed to have the last 2 weeks of September to move our things into the new place, but the maintenance guy didn’t finish things until the last week, and left such a huge mess, that it took me 2 days to clean up after him! OH! To add to the stress of moving, I’d had a spot on my leg for over a month, that initially I thought was a mosquito bite, but it wasn’t itchy, so I eventually forgot about it. Well, suddenly, one day at the beginning of October, it started to itch, then a day later, it got sore. The next day it started to swell! I went to the urgent care again, for this. The doctor’s assumption was an ingrown hair. She told me that she could not be sure, without cutting it open. But she gave me antibiotics (At this point, I’d pretty much been on some form of antibiotics for the past 4-6 months!). A couple days later, it had swollen to the size of a quarter, and was at least half an inch high. It could barely walk (oh yeah, it was just to the front of my inner thigh). Finally, I’d had enough. I burst it open, because the pressure was SO intense! Oh my goodness, the nasty puss that came out of that thing, and the amount of it. WOW! Immediate relief from the pressure. But now I had to keep it clean, by flushing with saline solution. Thankfully, I had some left from when I’d had the hickman line. There is still a mark, I don’t think it will ever go away.

November was ok. December was my birthday and Christmas. And the year is done. We are not doing any testing beyond blood work, unless/until my symptoms return.

OH, and after all the years of chemotherapy, radiation, stem cell transplant, etc. I am finally gone into menopause. These hot flashes and mood swings are awful, and I feel very sorry for my wonderful boyfriend. Thankfully, he is wonderful; he has been amazing through all this stuff. I appreciate him more than I could ever express.

Lymphoma And

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Lymphoma And Articles
The TNF receptor superfamily members are all type I membrane glycoproteins with typical homology in the extracellular domain of variable numbers of cysteine-rich repeats (overall homologies, 25% to 30%). In contrast, the TNF ligand superfamily members (with the exception of LT alpha) are type II membrane glycoproteins with homology to TNF in the extracellular domain (overall homologies, 20%). TNF and LT alpha are trimeric proteins and are composed of beta-strands forming a beta-jellyroll. The homology of the beta-strand regions for the TNF ligand superfamily members suggest a similar beta-sandwich structure and possible trimeric or multimeric complex formation for most or all members. A genetic linkage, as evidence for evolutionary relatedness, is found by chromosomal cluster of TNFR p80, CD30, 4–1BB, and OX40 for 1p36; TNFR p60, TNFR-RP, and CD27 for 12p13; TNF, LT alpha, and LT beta for 6 (MHC locus); CD27L and 4–1BBL for 19p13; and FASL and OX40L for 1q25. Of the TNF ligand superfamily, TNF, LT alpha, and LT beta and their receptors (TNFR p60, TNFR p80, and TNFR-RP) interact in a complex fashion of cross-binding. However, the other family members presently have a one ligand/one receptor binding principle (CD27/CD27L, CD30/CD30L, CD40/CD40L, 4–1BB/4–1BBL, OX40/gp34, and FAS/FASL). In general, the members of the TNF ligand superfamily mediate interaction between different hematopoietic cells, such as T cell/B cell, T cell/monocyte, and T cell/T cell. Signals can be transduced not only through the receptors but also through at least some of the ligands. The transduced signals can be stimulatory or inhibitory depending on the target cell or the activation state. Taken together, TNF superfamily ligands show for the immune response an involvement in the induction of cytokine secretion and the upregulation of adhesion molecules, activation antigens, and costimulatory proteins, all known to amplify stimulatory and regulatory signals. On the other hand, differences in the distribution, kinetics of induction, and requirements for induction support a defined role for each of the ligands for T-cell-mediated immune responses. The shedding of members of the TNF receptor superfamily could limit the signals mediated by the corresponding ligands as a functional regulatory mechanism. Induction of cytotoxic cell death, observed for TNF, LT alpha, CD30L, CD95L, and 4–1BBL, is another common functional feature of this cytokine family. Further studies have to identify unique versus redundant biologic and physiologic functions for each of the TNF superfamily ligands.(ABSTRACT TRUNCATED AT 400 WORDS)

Epstein-Barr virus (EBV)-specific DNA sequences were detected by polymerase chain reaction analysis in 15 of 47 (32%) DNA extracts prepared from CD30-positive (Ki-1 antigen-positive) anaplastic large cell (ALC) lymphomas. EBV-encoded RNA (EBER) transcripts could be detected by in situ hybridization in the tumor cells of 9 of 11 EBV DNA- positive cases. Twenty-eight cases were examined by immunohistology on cryostat sections for the presence of the EBV-encoded latent membrane protein (LMP), the nuclear antigen 2 (EBNA2), the BZLF1 transactivator protein, and the late viral glycoprotein gp350/250. A distinct LMP- specific membrane and cytoplasmic staining was detected exclusively in lymphoma cells of five cases (18%); two of these cases additionally expressed EBNA2. BZLF1 protein and gp350/250 immunoreactivity was absent in all instances. All LMP-positive cases contained EBV DNA and EBER sequences. The pattern of EBV latent protein expression in ALC lymphomas showed heterogeneity with respect to EBNA2 expression: LMP- positive/EBNA2-negative cases displayed a pattern previously described for undifferentiated nasopharyngeal carcinomas and Hodgkin's disease, whereas LMP-positive and EBNA2-positive cases showed parallels to lymphoblastoid cell lines. Because the LMP gene has transforming potential, our findings support the concept of a pathoetiologic role for EBV in a proportion of CD30-positive ALC lymphomas.


OBJECTIVE: To review recent studies of systemic therapy for mycosis fungoides and the S�zary syndrome (cutaneous T-cell lymphomas).

DATA SOURCES: English-language articles indexed in MEDLINE from 1988 through 1994.

STUDY SELECTION: All therapeutic studies were selected.

DATA EXTRACTION: The data were abstracted without judgments on response criteria or patient numbers. Data quality and validity were assessed by independent author reviews.

DATA SYNTHESIS: No systemic therapy cures patients with cutaneous T-cell lymphomas. Single and combined chemotherapeutic agents produce high response rates. Whether any of these is preferred is not established. A randomized trial comparing combination chemotherapy plus radiation therapy with topical therapy showed no survival benefit for the combination. Several adenosine analogs and retinoids were active, but their optimal use is uncertain. Interferons are as active as chemotherapeutic agents and may be less toxic. Interferon combined with psoralen plus ultraviolet A light therapy produces high complete response rates and long-lasting remissions. Combinations with other systemic therapies do not increase response rates. Photopheresis therapy should be regarded as experimental. Promising preliminary results were seen with interleukin-2 fusion toxins and several antibody conjugates.

CONCLUSIONS: Systemic therapy should be considered effective and palliative. The principles of treating all low-grade lymphomas can be applied. Randomized trials are needed to evaluate new agents (such as a comparison of psoralen plus ultraviolet light with or without interferon), and large phase II trials are needed for new agents such as photopheresis, interleukin-2 fusion toxin, temozolomide, and others.

Lymphomas

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Lymphomas Biography
Combination chemotherapy has transformed aggressive non-Hodgkin's lymphoma from a fatal disease into one that is often curable. However, many patients still die of their disease, underscoring the need for more accurate methods of prospectively identifying patients with different long-term prognoses. The identification of those at “high” or “low” risk could have important therapeutic implications. Patients at high risk who are not effectively treated with current regimens may benefit from new experimental approaches, whereas those at low risk may do well with standard therapy but sustain severe toxic reactions without additional benefit if they are treated with experimental regimens. The identification of different risk groups would also aid in the design and interpretation of therapeutic trials.

The tumor stage of patients with aggressive non-Hodgkin's lymphoma is currently determined with the Ann Arbor classification, which was originally developed for Hodgkin's disease1. This classification emphasizes the distribution of nodal disease sites because Hodgkin's disease commonly spreads through contiguous groups of lymph nodes1. Since the patterns of disease spread in Hodgkin's disease and non-Hodgkin's lymphoma are different, it is not surprising that the Ann Arbor classification system is less accurate in identifying prognostic subgroups of patients with aggressive non-Hodgkin's lymphoma2.
In previous analyses of relatively small numbers of patients with this disease, a variety of clinical characteristics were consistently associated with outcome: the age at diagnosis, the presence or absence of systemic (B) symptoms, performance status, the serum lactate dehydrogenase (LDH) concentration, the number of nodal and extranodal sites of disease, tumor size, and the distinction between localized disease (Ann Arbor stage I or II) and advanced disease (stage III or IV)3-13. These features were thought to reflect the tumor's growth and invasive potential (LDH level, tumor stage, tumor size, number of nodal and extranodal sites of disease, and the presence or absence of bone marrow involvement), the patient's response to the tumor (performance status and status for B symptoms), and the patient's ability to tolerate intensive therapy (performance status, bone marrow involvement, and age). Many investigators identified a subgroup of clinical features that remained independently significant in multivariate analyses of their patients and used this subgroup to develop prognostic models that would predict a given patient's risk of death4-11,13. Although the specific clinical features in these models differed, all models included the measurements of disease volume and extent of tumor involvement at presentation. To develop a better prognostic-factor model for aggressive non-Hodgkin's lymphoma, 16 institutions and cooperative groups in the United States, Europe, and Canada participated in the project.

METHODS
Characteristics of the Patients
Participating centers submitted data on each eligible patient included in electronic files.
Adult patients were eligible for this study if they had diffuse mixed, diffuse large-cell, or large-cell immunoblastic lymphoma (International Working Formulation14 categories F, G, and H); diffuse centroblastic-centrocytic, centroblastic, immunoblastic, or unclassified high-grade lymphoma (Kiel classification15); or diffuse mixed lymphocytic-histiocytic or diffuse histiocytic lymphoma (Rappaport classification16). All the patients were treated with a combination-chemotherapy regimen containing doxorubicin as part of a phase 2 or 3 study between 1982 and 1987. The inclusion of only patients who had completed therapy by 1987 ensured a minimum of 3 years of follow-up for all patients and a median of 4 1/2 years of follow-up for surviving patients. The stages of the tumors were determined and their pathologic characteristics were reviewed according to guidelines at the participating institutions.
The clinical features evaluated for potential prognostic importance were sex, age, tumor stage, performance status, B symptoms, sites of lymphomatous involvement, number of extranodal disease sites, size of the largest tumor, and serum concentrations of LDH, albumin, and beta2-microglobulin. The Ann Arbor stage of the tumor was designated as I, II non-bulky (largest tumor dimension, <10 cm), II bulky (largest dimension, ≥ 10 cm), III, or IV. Performance status was assessed according to the Eastern Cooperative Oncology Group scale, in which 0 indicated that the patient had no symptoms; 1, the patient had symptoms but was ambulatory; 2, the patient was bedridden less than half the day; 3, the patient was bedridden half the day or longer; and 4, the patient was chronically bedridden and required assistance with the activities of daily living. Performance status was classified as 0 or 1 (the patient was ambulatory) or 2, 3, or 4 (the patient was not ambulatory) (equivalent Karnofsky scores, ≥ 80 and ≤ 70). B symptoms were defined as recurrent fever (temperature, >38.3 °C [101 °F]), night sweats, or the loss of more than 10 percent of body weight. The recorded sites of extranodal lymphomatous involvement included the bone marrow, gastrointestinal tract, liver, lung, central nervous system, and other sites; the numbers of extranodal disease sites were recorded as 0, 1, or more than 1. Splenic involvement was also recorded. The largest dimension of the largest site of bulky disease was measured and reported as being less than 10 cm or as 10 cm or more. The serum LDH level was expressed as the ratio of the measured value to the upper limit of the normal range reported in the laboratory of each participating institution.

Assessment of Response
A complete response to treatment was defined by the participating institutions as the disappearance of all clinical evidence of disease and the normalization of all laboratory values and radiographic results that had been abnormal before treatment. The relapse-free survival of patients with complete responses was measured as the interval between the end of treatment and relapse or death or the date of the last follow-up evaluation in patients who had no relapse. Survival was measured as the interval between the beginning of treatment and death or the date of the last follow-up evaluation.
Statistical Analysis
The univariate associations between response and individual clinical features were analyzed with Fisher's exact test for two-by-k tables17. Relapse-free survival among patients with complete responses and overall survival among all patients were estimated with the method of Kaplan and Meier18. The univariate associations between individual clinical features and overall survival and relapse-free survival were determined with the log-rank test19.

Since all centers had not originally gathered all the requested information on their patients, data on several prognostic factors were missing from the patients' files. No data on outcome were missing. Missing data were dealt with by carrying out “complete case” analyses, in which patients were excluded from particular analyses if their files did not contain data on the required variables. This method did not bias analysis, since the availability of data at each center was determined by the data collection at the time of treatment rather than by the eventual outcome.

Features independently associated with overall survival and relapse-free survival were identified in multivariate analyses by proportional-hazards regression20. Step-down regression methods were used to build parsimonious statistical models for the association of prognostic factors with overall survival and relapse-free survival among patients with complete responses. Time-dependent death rates (hazard functions) were estimated according to the nonparametric kernel smoothing methods of Gray21.

RESULTS
Univariate Analysis of Predictive Features
The presenting characteristics of the 3273 patients with tumors in Ann Arbor stages I through IV who were included in the analysis are shown in Table 1TABLE 1
Characteristics of 3273 Patients Presenting with Aggressive Non-Hodgkin's Lymphoma.
. Of these patients, 66 percent had complete responses. The five-year relapse-free survival rate among the patients with complete responses was 59 percent, and the five-year overall survival among all patients was 52 percent (Table 2TABLE 2
Outcome According to the Patients' Characteristics.
). The associations between the patients' characteristics and the response rate, relapse-free survival among those with complete responses, and overall survival are shown in Table 2. Given the size of the study population, it is not surprising that the majority of the listed clinical characteristics were significantly associated with outcome.
Independent Prognostic Factors and the Prognostic-Factor Model
Information on seven prognostic factors (age at diagnosis, performance status, serum LDH level, Ann Arbor stage, tumor size, number of extranodal disease sites, and presence or absence of B symptoms) that had been associated with outcome in many previous studies3-13 was complete for 1872 patients, of whom 1385 (74 percent) were randomly selected as a training sample in which to identify independent prognostic factors to form a model. A training sample of nearly 75 percent was chosen because it would be large enough to detect a 20 percent increase in the relative risk of death associated with even a relatively rare characteristic.
The step-down regression analysis of overall survival in the training sample evaluated 12 variables: the 7 prognostic factors mentioned above, 4 individual sites of extranodal disease (bone marrow, liver, lung, and central nervous system), and the spleen. These 12 variables included all those in our data set except sex (which was not associated with survival), gastrointestinal involvement (which had a statistically significant but clinically unimportant association with survival [Table 2]), and serum beta2-microglobulin and albumin levels (on which we had insufficient data). In the regression analysis, age was coded as 60 years or less or more than 60 years because this dichotomy was most commonly used in previous analyses and because patients 60 or younger were the most likely candidates for intensive experimental therapy. The Ann Arbor stage and the number of extranodal disease sites were coded so that the individual categories and all natural dichotomous groupings for each variable were included (e.g., Ann Arbor stage I vs. II vs. III vs. IV; stage I vs. stages II through IV; stage I or II non-bulky disease vs. stage II bulky disease, stage III, or stage IV; and stage I or II vs. stage III or IV.) The most discriminating cutoff point for serum LDH was determined by applying classification and regression trees (which separate patients into homogeneous subgroups)22 to martingale residuals (the differences between the number of events observed and the number predicted by the model)23. The most predictive cutoff point for LDH was a level 1.2 times normal (≤ 1.2 times normal vs. >1.2 times normal) in both univariate and multivariate analyses; however, a level 1 times normal (≤ 1 vs. >1) was chosen as the cutoff point because it was almost as predictive as 1.2 times normal and easier to use.
The five pretreatment characteristics that remained independently significant in the analysis of the training sample were age (≤ 60 vs. >60 years), tumor stage (stage I or II [localized disease] vs. stage III or IV [advanced disease]), the number of extranodal sites of disease (≤ 1 vs. >1), performance status (0 or 1 vs. ≥ 2), and serum LDH level (≤ 1 times normal vs. >1 times normal) (Table 3TABLE 3
Factors Independently Prognostic of Overall Survival in the Training Sample.

). These five features were used to design a model to predict an individual patient's risk of death -- the international index. Since the relative risks associated with each of the independently significant risk factors were comparable (Table 3), the relative risk of death could be characterized by summing the number of risk factors present at diagnosis. Risk groups were defined by comparing the relative risk of death in patients with each possible number of presenting risk factors (0, 1, 2, 3, 4, or 5) and combining categories with similar relative risks (e.g., 0 with 1 or 4 with 5). Patients were then assigned to one of four risk groups on the basis of their number of presenting risk factors: 0 or 1, low risk; 2, low intermediate risk; 3, high intermediate risk; or 4 or 5, high risk. The survival curves and death rates over time for the four risk groups in the training sample are shown in Figure 1FIGURE 1
Survival According to Risk Group Defined by the International Index.
. To provide a basis for comparison, the survival curve and death rate for all 3273 patients in the study are also included (Figure 1).
The prognostic-factor model was then applied to a validation sample of patients, which contained the remaining patients with complete data on the seven specified variables (487 of the 1872 patients with complete data) and the other patients with complete data on only the five variables in the final model (159 additional patients; total, 646). The model was equally predictive in the validation sample, identifying four groups of patients at low, low intermediate, high intermediate, or high risk of death (Figure 1). In the training and validation samples, the risk of death was increased primarily in the first three to four years after diagnosis (Figure 1, right panels).
Since the training and validation samples had comparable outcomes, we combined these two groups into a single group for further detailed analysis (Figure 1, bottom panels; Table 4TABLE 4
Outcome According to Risk Group Defined by the International Index and the Age-Adjusted International Index.
, international index, all patients). The four risk groups had distinctly different rates of complete response, relapse-free survival, and overall survival (Table 4). For example, the low-risk group had a complete-response rate of 87 percent and a five-year overall survival of 73 percent, whereas the high-risk group had a complete-response rate of only 44 percent and a five-year overall survival of only 26 percent (Table 4, international index, all patients).

The Significance of Age in Prognosis
Since the two age groups (≤ 60 vs. >60 years) had significantly different outcomes (Table 2 and Table 3) and the age limit for patients treated by most intensive experimental regimens for non-Hodgkin's lymphoma is 60 years, we also developed an age-adjusted model for younger patients -- the age-adjusted international index. Three of the previously identified risk factors -- tumor stage, performance status, and LDH level -- remained independently significant prognostic factors among the patients in the training sample who were 60 or younger (885 patients) (Table 3). Since the relative risks of death associated with the three risk factors were comparable (Table 3), a younger patient could also be assigned to a risk group by counting the number of risk factors present at diagnosis. The age-adjusted international index was similarly predictive in the training and validation samples (in 885 and 389 patients, respectively, or a total of 1274), justifying our combining these two groups for further analysis (Figure 2FIGURE 2
Survival among the 1274 Younger Patients (≤ 60 Years) According to Risk Group Defined by the Age-Adjusted International Index.

; Table 4, age-adjusted index, patients ≤ 60). The younger patients (≤ 60 years) were assigned to four risk groups according to the number of risk factors at presentation (0, 1, 2, or 3) (Figure 2 and Table 4). The younger patients in the low-risk group had a complete-response rate of 92 percent and a five-year overall survival of 83 percent, whereas those in the high-risk group had a complete-response rate of only 46 percent and a five-year overall survival of only 32 percent (Table 4). As was true of all patients (Table 4, international index, all patients), the increased risk of death among the younger patients was due to both a lower complete-response rate and lower relapse-free survival among those with complete responses.

To define the differences between the younger and older patients more specifically, the two age groups were compared by the age-adjusted international index (Table 4). The distribution of the younger patients among the four risk groups was similar to the distribution of the older patients among these groups (Table 4). Although the older patients (>60 years) had complete-response rates that were similar to or only slightly lower than those of the younger patients, the older patients with complete responses had much lower rates of relapse-free survival (Table 4). These data suggested that increased numbers of older patients died of lymphoma rather than of unrelated causes. Consistent with this observation was the finding that the older patients also had an observed death rate that was substantially higher than that of an age-matched cohort (data not shown)24.

Relapse-free Survival among Patients with Complete Responses
If patients with an increased risk of relapse from complete response could be identified before relapse, they might be candidates for experimental approaches to consolidation therapy, such as high-dose chemoradiotherapy with infusion of peripheral-blood stem cells or bone marrow support. For this reason, we also identified the presenting clinical features most closely associated with the risk of relapse from complete response: age (≤ 60 vs. >60 years: relative risk, 1.80; P<0.001), tumor stage (I or II vs. III or IV: relative risk, 1.79; P<0.001), and serum LDH level (≤ 1 times normal vs. >1 times normal: relative risk, 1.47; P<0.001).

International Index and Ann Arbor Stage
Since features other than the Ann Arbor stage were independently associated with overall survival in our analyses (Table 3), a model incorporating these additional features would by definition be more predictive than the Ann Arbor classification system. This is illustrated in Figure 3FIGURE 3
Survival among 1880 Patients in Ann Arbor Stages II, III, and IV, According to Risk Group Defined by the International Index.
, which shows the survival of patients in Ann Arbor stage II, III, and IV according to their risk group as defined by the international index.

DISCUSSION
The goal of our project was to develop a system for classifying patients with aggressive non-Hodgkin's lymphoma according to universally recognized clinical features. The resulting model applicable to all these patients (the international index) incorporates clinical features that reflect the growth and invasive potential of the tumor (tumor stage, serum LDH level, and number of extranodal disease sites), the patient's response to the tumor (performance status), and the patient's ability to tolerate intensive therapy (age and performance status). The simplified model for younger patients (the age-adjusted international index) uses a subgroup of these clinical features (tumor stage, LDH level, and performance status). Both models identified four risk groups of patients based on both the rate of complete response and the rate of relapse from complete response. The size of the study population and the diversity of the referring institutions and study centers helped ensure that the international index and the age-adjusted index were derived from a broadly representative group. Since recent studies indicate that unselected patients with aggressive non-Hodgkin's lymphoma who are treated with first-, second-, and third-generation chemotherapy regimens have comparable outcomes,25-27 the variety of regimens that contained doxorubicin in our study is unlikely to have influenced the analysis. Furthermore, the international index was equally predictive of survival in two recent series of over 2000 patients treated with intensive third-generation regimens25 (and unpublished data).

We developed separate models -- one for all patients (the international index) and one for younger patients (the age-adjusted international index) -- because the two models may be applicable in different settings. In trials that include patients of all ages, the international index, not restricted according to age, would be more useful. However, in trials of more intensive experimental approaches that are targeted to younger patients, the age-adjusted index could be used.

We retained four risk groups of patients defined by the international index and the age-adjusted index because physicians and investigators may collapse these risk groups differently, depending on their objectives. For example, if the goal is to compare the types of patients who are being treated in specific trials, the relative numbers of patients in all four risk groups should be noted. If the objective is to identify candidates for experimental therapy -- patients whose predicted five-year survival is less than 50 percent with standard regimens -- it would be reasonable to include patients identified as being at high, high intermediate, and perhaps even low intermediate risk according to the international index (Table 4). However, when experimental approaches are specifically designed for younger patients (≤ 60 years), the target population might be patients at high intermediate and high risk as defined by the age-adjusted international index (Table 4). It is important that the target population of a “high-risk” protocol be accurately defined because the results of an experimental approach may be as dependent on the definition of high risk as on the regimen itself28,29. Furthermore, therapeutic approaches should be compared in appropriate, age-matched populations because younger patients generally have more favorable outcomes.

If it were possible to identify patients who enter complete remission but are at increased risk of subsequent relapse, such patients might be candidates for intensive experimental consolidation therapy. However, in our study, the clinical features that correlated with an increased risk of relapse were also associated with a decreased likelihood of obtaining an initial complete remission. Therefore, therapeutic approaches to patients at high risk must be directed toward increasing the low rates of initial complete responses as well as toward improving the durability of those responses.

Although the international index was specifically developed to predict outcome in patients with aggressive non-Hodgkin's lymphoma, it may also have prognostic value in patients with lymphoma that is histologically more indolent. Recent studies indicate that a prognostic-factor model developed for patients with aggressive non-Hodgkin's lymphoma also predicted survival in a small series of patients with follicular lymphoma,30 and that the international index predicted survival in a larger series of similar patients (unpublished data).

Finally, it is important to recognize that the clinical prognostic features incorporated in the international index are, in part, surrogate variables that reflect the biologic heterogeneity of aggressive non-Hodgkin's lymphoma. As additional features such as serologic variables (beta2-microglobulin level31), indexes of tumor-cell proliferation (expression of Ki-67 antigen32 and incorporation of tritiated thymidine33), karyotypic abnormalities,34-37 and aberrant adhesion-molecule38,39 and oncogene40 expression are evaluated in larger numbers of patients, the biologic heterogeneity of this disease may be better understood. In the meantime, clinical prognostic-factor models such as the international index and the age-adjusted index can be used to identify specific risk groups and to compare different therapeutic approaches.

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Lymphoma Lymphoma

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Lymphoma Lymphoma Articles
Lymphoma is the most common blood cancer. The two main forms of lymphoma are Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). Lymphoma occurs when lymphocytes, a type of white blood cell, grow abnormally. The body has two main types of lymphocytes that can develop into lymphomas: B-lymphocytes (B-cells) and T-lymphocytes (T-cells). Cancerous lymphocytes can travel to many parts of the body, including the lymph nodes, spleen, bone marrow, blood or other organs, and can accumulate to form tumors.

Non-Hodgkin lymphoma is the most common cancer of the lymphatic system, a part of the immune system. Since the early 1970’s, incidence rates for NHL have nearly doubled. Of the nearly 500,000 Americans with lymphoma, approximately 332,000 have this form. Over 65,000 cases of NHL are diagnosed annually in the United States.

Non-Hodgkin lymphoma is not a single disease, but rather a group of several closely related cancers. The World Health Organization estimates that there are at least 61 types of NHL. Although the various types of NHL have some things in common, they differ in their appearance under the microscope, their molecular features, their growth patterns, their impact on the body and how they are treated.
Non-Hodgkin lymphomas are broadly divided into two major groups: B-cell lymphomas and T-cell lymphomas. B-cell lymphomas develop from abnormal B-lymphocytes and account for 85 percent of all NHLs. T-cell lymphomas develop from abnormal T-lymphocytes and account for the remaining 15 percent of all NHLs. Non-Hodgkin lymphomas may also be classified as indolent (slow-growing) or aggressive (fast-growing).

Symptoms
Common signs and symptoms of NHL include swelling of the lymph nodes (which is often but not always painless), fever, night sweats, unexplained weight loss and lack of energy. While most people who have these complaints will not have NHL, anyone with persistent symptoms should be seen by a physician to make sure that lymphoma is not present.

Risk Factors
The causes of NHL remain unknown, however, risk for develop­ing lymphoma may be higher in individuals who:
•      have a family history of NHL (though no hereditary pattern has been well established)
•      are affected with an autoimmune disease
•      have received an organ transplant
•      have been exposed to chemicals such as pesticides, fertil­izers or organic solvents for a long period
•      have been infected with viruses such as Epstein-Barr, human T-lymphotropic virus type 1 (HTLV-1), HIV/AIDS, hepatitis C or certain bacteria, such as H-pylori

Stages
Non-Hodgkin lymphoma is divided into four stages based on how far the disease has spread.
•      Stage I (early disease): the cancer is found only in a single lymph node OR in one organ or area outside the lymph node.
•      Stage II (locally advanced disease): the cancer is found in two or more lymph node regions on one side of the diaphragm.
•      Stage III (advanced disease): the cancer involves lymph nodes both above and below the diaphragm.
•      Stage IV (widespread disease): the cancer is found in several parts of one or more organs or tissues (in addition to the lymph nodes). Or, it is in the liver, blood or bone marrow.

Treatment Options
Many effective treatment options exist for NHL patients, including:

•      watchful waiting
•      chemotherapy
•      radiation therapy
•      stem cell transplantation
•      novel targeted agents
•      newer versions of established agents

The form of treatment chosen depends on the type of lymphoma and the stage of disease, as well as other factors including age, prior therapies received and the patient’s overall health.

Some patients may relapse (disease returns after treatment) or become refractory (disease does not respond to treatment). However, numerous treatment options exist for patients with relapsed or refractory NHL, which are often referred to as secondary therapies. Many of the novel therapeutic agents that have been approved by the United States Food and Drug Administration, as well as those being investigated in clinical trials, focus specifically on those with relapsed or refractory disease.

Before starting treatment, patients should discuss all available treatment options with their physician.


AIDS-Related Lymphomas
Lymphomas occurring in HIV-positive patients are usually aggressive. It is estimated that as many as ten percent of people who are HIV-positive will ultimately develop lymphoma. Although both Hodgkin and non-Hodgkin lymphomas may occur in AIDS patients, non-Hodgkin lymphomas are more common and include diffuse large B-cell, Burkitt’s/Burkitt-like and primary central nervous system lymphoma.

Anaplastic Large-Cell Lymphoma
Anaplastic large-cell lymphoma (ALCL) is a rare type of aggressive T-cell lymphoma comprising about 3 percent of all lymphomas in adults and between 10 percent and 30 percent of all lymphomas in children.

Angioimmunoblastic Lymphoma 
Angioimmunoblastic lymphoma (AILD) is a fast-growing T-cell lymphoma that accounts for between one percent and two percent of all cases of NHL in the United States.

Blastic NK-Cell Lymphoma
Blastic NK-cell lymphoma is a very rare T-cell lymphoma, affecting only a few people (usually adults) each year. This lymphoma is very fast growing, is difficult to treat and can arise anywhere in the body. Since this disease is so rare, patients should consult with their medical team to find promising therapies or clinical trials.

Burkitt's Lymphoma, Burkitt-like Lymphoma (Small Non-Cleaved Cell Lymphoma)
Burkitt's lymphoma is an aggressive B-cell form of NHL that occurs most often in children and young adults. There are three main types of Burkitt’s lymphoma: sporadic, endemic and immunodeficiency-related disease. While sporadic Burkitt’s lymphoma occurs throughout most of the world, endemic Burkitt's lymphoma is found mostly in Africa and is often associated with the Epstein-Barr virus (EBV). Immunodeficiency-related Burkitt's lymphoma is diagnosed most often in people infected with HIV/AIDS. The disease may affect the jaw, central nervous system, bone marrow, bowel, kidneys, ovaries or other organs. Burkitt's lymphoma has a specific chromosomal abnormality called the t(8;14) translocation and behaves aggressively. Burkitt's lymphoma is potentially curable.

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
According to the American Cancer Society, approximately 15,000 new cases of CLL and 3,600 new cases of SLL are diagnosed annually.

Cutaneous T-Cell Lymphoma
Cutaneous T-cell lymphomas (CTCL) arise in the skin and account for approximately two percent to three percent of all NHL cases.

Diffuse Large B-Cell Lymphoma
Diffuse large B-cell lymphoma (DLBCL) is the most common form of NHL, accounting for up to one-third of newly diagnosed cases.

Enteropathy-Type T-Cell Lymphoma
Enteropathy-type T-cell lymphoma is an extremely rare subtype of T-cell lymphoma that appears in the intestines and is strongly associated with celiac disease. As with other rare cancers, patients should discuss treatment options with their medical team.

Follicular Lymphoma
Follicular lymphoma is a relatively common lymphoma, making up between 20 percent and 30 percent of all NHLs, and typically occurs in middle-aged and older adults, but it can affect younger people in their 30s and 40s.

Hepatosplenic Gamma-Delta T-Cell Lymphoma
Hepatosplenic gamma-delta T-cell lymphoma is an extremely rare and aggressive disease that starts in the liver or spleen. This lymphoma may occur in people with Crohn’s disease whose immune system is suppressed. As with other rare cancers, patients should discuss treatment options with their medical team.

Lymphoblastic Lymphoma
Lymphoblastic lymphoma can appear in both B-cells and T-cells, but is much more common in T-cells, comprising 80 percent of all lymphoblastic lymphomas. This lymphoma is most often diagnosed in children. With intensive chemotherapy, the complete remission rate can be very high. The disease is often treated similarly to acute lymphoblastic leukemia.

Marginal Zone Lymphoma
Marginal zone B-cell lymphomas, a group of indolent lymphomas whose cells come from B-lymphocytes normally found in the marginal zone of the secondary lymphoid follicles in the spleen and lymph nodes, accounts for approximately seven percent of all NHLs. The median age for diagnosis of this type of lymphoma is 65. Marginal zone lymphomas encompass three basic types: (1) extranodal or mucosa-associated lymphoid tissue (MALT), occurring outside the lymph nodes, (2) nodal, occurring within the lymph nodes, and (3) splenic, occurring mostly in the spleen and blood. Skin-associated lymphoid-tissue-related B-cell lymphoma (SALT) is also considered a form of MALT lymphoma. Marginal zone and MALT lymphomas vary from other types of B-cell NHLs in a number of ways: (1) their natural history is different; (2) many people who develop MALT lymphoma have a history of inflammation or autoimmune disorders; (3) chronic inflammation is associated with Helicobacter pylori (H. pylori), a microbial pathogen linked to chronic gastritis; and, (4) sometimes, MALT lymphomas can be treated with antibiotics. Different infections have also been implicated in other forms of MALT lymphoma. Hepatitis C has been associated with splenic marginal zone lymphoma. Nodal marginal zone B-cell lymphomas are uncommon and are sometimes called monocytoid B-cell lymphomas.

Nasal T-Cell Lymphoma
Although this fast-growing lymphoma is very rare in the United States, it is relatively common in Asia and parts of Latin America, leading researchers to suspect that some ethnic groups may be more prone to this cancer, which affects both children and adults. This type of lymphoma is associated with the Epstein-Barr virus. As with other rare cancers, patients should consult with their medical team for treatment options and the availability of clinical trials.

Pediatric Lymphoma
Childhood NHL comprises about five percent of all NHL cases diagnosed in the United States. The most common types are lymphoblastic lymphoma, Burkitt’s lymphoma, diffuse large B-cell lymphoma and anaplastic large-cell lymphoma. Lymphoblastic lymphoma is closely related to childhood acute lymphoblastic leukemia. The number of children with NHL continues to increase.

Peripheral T-Cell Lymphomas
Peripheral T-cell lymphomas (PTCL) refer to a large number of different T-cell lymphomas that together comprise between 10 percent and 15 percent of all NHL cases and can occur anytime during adulthood.

Primary Central Nervous System Lymphoma
Primary central nervous system lymphoma (PCNSL) is a type of cancer that is limited to the brain or spinal cord but may also be found in tissues around the eye. An increasing occurrence of this disease has been seen in patients with AIDS and others whose immune system has been compromised. Median age of diagnosis for patients with PCNSL is 55 years for patients with a normal immune system and 31 years for AIDS patients. Although in the past the outlook for patients with this cancer has been poor, today, the survival rate has greatly improved.

T-Cell Leukemias
T-cell leukemias are also derived from T-cells and can act like T-cell lymphoma. These cancers include T-cell promyelocytic leukemia, T-cell granular lymphocytic leukemia, aggressive NK-cell leukemia and adult T-cell lymphoma/leukemia.

Transformed Lymphomas
Although indolent B-cell lymphomas, such as follicular lymphomas, are most commonly associated with transforming to aggressive disease, slow-growing T-cell lymphomas can also progress to aggressive disease.

Treatment-Related T-Cell Lymphomas
Treatment-related T-cell lymphomas may appear after solid organ or bone marrow transplantation. The immune system suppression that is required for transplant patients can put them at risk for developing post-transplant lymphoproliferative disorders, certain unusual forms of peripheral T-cell lymphoma and other types of NHL. Treatment-related T-cell lymphomas may require therapy that differs from the standard treatments normally used to treat these conditions.

Waldenstrom's Macroglobulinemia
Waldenstrom’s macroglobulinemia (also known as lymphoplasmacytic lymphoma or immunocytoma) is a rare B-cell lymphoma that occurs in less than two percent of people with NHL.