Mantle cell lymphoma
Encyclopedia
Mantle cell lymphoma is one of the rarest of the non-Hodgkin's lymphomas
(NHLs), comprising about 6% of NHL cases. There are only about 15,000 patients presently in the U.S. (The prevalence seems to be somewhat higher in Europe.) While it is difficult to treat and seldom considered cured, investigations into better treatments are actively pursued worldwide. Median survival times were about 3 years, but are now estimated as approaching 6 years for new patients.
MCL is a subtype of B-cell lymphoma, due to CD5
positive antigen-naive pregerminal center B-cell within the mantle zone
that surrounds normal germinal center follicles. MCL cells generally over-express cyclin D1
due to a t(11:14) chromosomal translocation
in the DNA
. More specifically, the translocation is at t(11;14)(q13;q32).
The cause is unknown and no inherited predisposition has been identified. MCL is not communicable. Essentially, it is an abnormal break and subsequent translocation in a gene
that causes the cells to divide too early before becoming capable of helping to fight diseases. In addition, the cells do not die as they should and therefore accumulate in the lymphoid system, including lymph nodes and the spleen, with non-useful cells eventually rendering the system dysfunctional. MCL affected cells proliferate in a nodular or diffuse pattern with two main cytologic variants: typical or blastic. Typical cases are small to intermediate sized cells with irregular nuclei. Blastic (aka blastoid) variants have intermediate to large sized cells with finely dispersed chromatin
and are more aggressive in nature.
It is common for a person to have initially noticed "a bump" on the neck or in the armpits or groin.
(PCR) and CER3 clonotypic primers are additional methods, but are less often used.
The immunophenotype profile consists of CD5+ (in about 80%), CD10-/+,It is usually CD5
+ and CD10-. CD20+, CD23-/+ (though plus in rare cases). Generally, cyclin D1 is expressed but it may not be required. The workup for Mantle cell lymphoma is similar to the workup for many indolent lymphomas and certain aggressive lymphomas.
Mantle cell lymphoma is a systemic disease with frequent involvement of the bone marrow and gastrointestinal tract (generally showing polyposis in the lining). There is also a not-uncommon leukemic phase, marked by presence in the blood. For this reason, both the peripheral blood and bone marrow are evaluated for the presence of malignant cells. Chest, abdominal, and pelvic CT scans are routinely performed.
Since mantle cell lymphoma may present a lymphomatous polyposis coli and colon involvement is common, colonoscopy is now considered a routine part of the evaluation. Upper endoscopy and neck CT scan may be helpful in selected cases. In some patients with the blastic variant, lumbar puncture is done to evaluate the spinal fluid for involvement.
Prognosis for individuals with MCL is problematic and indexes do not work as well due to patients presenting with advanced stage disease. Staging is used but is not very informative, since the malignant B-cells can travel freely though the lymphatic system and therefore most patients are at stage III or IV at diagnosis. Prognosis is not strongly affected by staging in MCL and the concept of metastasis does not really apply.
The Mantle Cell Lymphoma International Prognostic Index (MIPI) was derived from a data set of 455 advanced stage MCL patients treated in series of clinical trials in Germany/Europe. Of the evaluable population, approximately 18% were treated with high-dose therapy and stem cell transplantation in first remission. The MIPI is able to classify patients into three risk groups: low risk (median survival not reached after median 32 mos follow-up and 5-year OS rate of 60%), intermediate risk (median survival 51 months) and high risk (median survival 29 months). In addition to the 4 independent prognostic factors included in the model, the cell proliferation index (Ki-67) was also shown to have additional prognostic relevance. When the Ki67 is available, a biologic MIPI can be calculated.
(The letter A after the Roman numeral indicates that normal external symptoms are not present. The Letter B indicates the symptoms are present and hence they are called “B Symptoms”.)
MCL is one of the few NHLs that can cross the boundary into the brain, yet it can be treated in that event.
There are a number of prognostic indicators that have been studied. There is not universal agreement on their importance or usefulness in prognosis.
Ki-67
is an indicator of how fast cells mature and is expressed in a range from about 10% to 90%. The lower the percentage, the lower the speed of maturity, and the more indolent the disease. Katzenberger et al. Blood 2006;107:3407 graphs survival versus time for subsets of patients with varying Ki-67 indices. He shows median survival times of about one year for 61-90% Ki-67 and nearly 4 years for 5-20% Ki-67 index.
MCL cell types can aid in prognosis in a subjective way. Blastic is a larger cell type. Diffuse is spread through the node. Nodular are small groups of collected cells spread through the node. Diffuse and nodular are similar in behavior. Blastic is faster growing and it is harder to get long remissions. Some thought is that given a long time, some non-blastic MCL transforms to blastic. Although survival of most blastic patients is shorter, some data shows that 25% of blastic MCL patients survive to 5 years. That is longer than diffuse type and almost as long as nodular (almost 7 yrs).
Beta-2 microglobulin
is another risk factor in MCL used primarily for transplant patients. Values less than 3 have yielded 95% overall survival to 6 yrs for auto SCT where over 3 yields a median of 44 mos overall survival for auto SCT (Khouri 03). This is not yet fully validated.
Testing for high levels of LDH
in NHL patients is useful because LDH is released when body tissues break down for any reason. While it cannot be used as a sole means of diagnosing NHL, it is a surrogate for tracking tumor burden in those diagnosed by other means. The normal range is approximately 100-190.
PET scans are much more effective when the information from them is integrated with that from a CT scan to show more precisely where the cancer activity is located and to more accurately measure the size of tumors.
There are four classes of treatments currently in general use: chemotherapy, immune based therapy, radioimmunotherapy and new biologic agents. The phases of treatment are generally: frontline, following diagnosis, consolidation, after frontline response (to prolong remissions), and relapse. Relapse is usually experienced multiple times.
is widely used as frontline treatment, and often is not repeated in relapse due to side effects. Alternate chemotherapy is sometimes used at first relapse. For frontline treatment, CHOP
with rituximab
(Rituxan, Mabthera) is the most common chemotherapy, and often given as outpatient by IV. A stronger chemotherapy with greater side effects (mostly hematologic) is HyperCVAD
, often given as in-patient, with rituximab and generally to fitter patients (some of which are over 65). HyperCVAD is becoming popular and showing promising results, especially with rituximab. It can be used on some elderly (over 65) patients, but seems only beneficial when the baseline Beta-2-MG blood test was normal. It is showing better complete remissions (CR) and progression free survival (PFS) than CHOP regimens. Another chemotherapy class is fludarabine
monotherapy, sometimes combined with cyclophosphamide and mitoxantrone, usually with rituximab. Cladribine
and clofarabine
are two other drugs being investigated in MCL. Cytotoxic chemotherapies, including bendamustin, are being studied alone and with similar combinations. A relatively new regimen that uses old drugs is PEP-C, which includes relatively small, daily doses of prednisone
, etoposide
, procarbazine
, and cyclophosphamide
, taken orally, has proven effective for relapsed patients. According to John Leonard M.D., a key researcher/proponent of PEP-C, may have anti-angiogenetic properties, something that he and his colleagues are testing through an ongoing drug trial.
Another approach involves using very high doses of chemotherapy, sometimes combined with total body irradiation
(TBI), in an attempt to destroy all evidence of the disease. The downside to this is the destruction of the patients' entire immune system as well, requiring rescue by transplantation of a new immune system (Hematopoietic stem cell transplantation), using either ones' own previously treated and stored stem cells (an autologous stem cell transplant), or those from a matched donor (an allogeneic stem cell transplant). A presentation at the December 2007 American Society of Hematology (ASH) conference by Christian Geisler, chairman of the Nordic Lymphoma Group (Copenhagen, Denmark), claimed that according to trial results, mantle cell lymphoma is potentially curable with very intensive chemo-immunotherapy followed by a stem cell transplant, when treated upon first presentation of the disease.
is dominated now by the oft used and effective rituximab
monoclonal antibody, sold under the trade name Rituxan (or as Mabthera in Europe and Australia). Some say it is a landmark in medicine . Rituximab can have good activity against MCL alone but especially in combination with chemotherapies to prolong response duration. Rituximab essentially tags the cancer cells for destruction by the body. There are newer variations on monoclonal antibodies combined with radioactive molecules known as Radioimmunotherapy
(RIT). These include Zevalin and Bexxar. Rituximab has also been used in small numbers of patients in combination with thalidomide
with some effect.
It will be fruitful to investigate the use of Bexxar as first line treatment. This treatment appears to be less tiring for patients, since it consists of two injections at a distance of a week, while most other treatments consist of 6-8 cycles of chemotherapy combined with Rituximab.
In contrast to these antibody-based 'passive' immunotherapies, the field of 'active' immunotherapy tries to reprogram a patient's immune system to specifically recognize and eliminate their own tumor cells. Examples of active immunotherapy include cancer vaccine
s, adoptive cell transfer
, and immunotransplant
, which combines vaccination and autologous stem cell transplant. Though no active immunotherapies are currently a standard of care, numerous clinical trial
s are ongoing.
, 6% of cases are mantle cell lymphoma.
Non-Hodgkin lymphoma
The non-Hodgkin lymphomas are a diverse group of blood cancers that include any kind of lymphoma except Hodgkin's lymphomas. Types of NHL vary significantly in their severity, from indolent to very aggressive....
(NHLs), comprising about 6% of NHL cases. There are only about 15,000 patients presently in the U.S. (The prevalence seems to be somewhat higher in Europe.) While it is difficult to treat and seldom considered cured, investigations into better treatments are actively pursued worldwide. Median survival times were about 3 years, but are now estimated as approaching 6 years for new patients.
MCL is a subtype of B-cell lymphoma, due to CD5
CD5 (protein)
CD5 is a cluster of differentiation found on a subset of IgM-secreting B cells called B-1 cells, and also on T cells. B-1 cells have limited diversity of their B-cell receptor due to their lack of the enzyme terminal deoxynucleotidyl transferase and are potentially self-reactive...
positive antigen-naive pregerminal center B-cell within the mantle zone
Mantle zone
The mantle zone of a lymphatic nodule is an outer ring of small lymphocytes surrounding a germinal center.It is also known as the "corona".It contains transient lymphocytes....
that surrounds normal germinal center follicles. MCL cells generally over-express cyclin D1
Cyclin D1
G1/S-specific cyclin-D1 is a protein that in humans is encoded by the CCND1 gene.Immunohistochemical staining of cyclin D1 antibodies is used to diagnose mantle cell lymphoma.-Interactions:...
due to a t(11:14) chromosomal translocation
Chromosomal translocation
In genetics, a chromosome translocation is a chromosome abnormality caused by rearrangement of parts between nonhomologous chromosomes. A gene fusion may be created when the translocation joins two otherwise separated genes, the occurrence of which is common in cancer. It is detected on...
in the DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
. More specifically, the translocation is at t(11;14)(q13;q32).
The cause is unknown and no inherited predisposition has been identified. MCL is not communicable. Essentially, it is an abnormal break and subsequent translocation in a gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
that causes the cells to divide too early before becoming capable of helping to fight diseases. In addition, the cells do not die as they should and therefore accumulate in the lymphoid system, including lymph nodes and the spleen, with non-useful cells eventually rendering the system dysfunctional. MCL affected cells proliferate in a nodular or diffuse pattern with two main cytologic variants: typical or blastic. Typical cases are small to intermediate sized cells with irregular nuclei. Blastic (aka blastoid) variants have intermediate to large sized cells with finely dispersed chromatin
Chromatin
Chromatin is the combination of DNA and proteins that make up the contents of the nucleus of a cell. The primary functions of chromatin are; to package DNA into a smaller volume to fit in the cell, to strengthen the DNA to allow mitosis and meiosis and prevent DNA damage, and to control gene...
and are more aggressive in nature.
Symptoms
The ratio of males to females affected is about 4:1. At diagnosis, typical patients are in their 60s and usually present to the oncologist with advanced disease. About half have either fever, heavy night sweats, unexplained weight loss (over 10%) or some combination. Swelling of lymph nodes and spleen are usually present. Bone marrow, liver and GI tract involvement occurs in a very high percentage.It is common for a person to have initially noticed "a bump" on the neck or in the armpits or groin.
Diagnosis
Diagnosis generally requires stained slides of a surgically removed part of a lymph node. Other methods are also commonly used, including cytogenetics and fluorescence in situ hybridization (FISH). Polymerase chain reactionPolymerase chain reaction
The polymerase chain reaction is a scientific technique in molecular biology to amplify a single or a few copies of a piece of DNA across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence....
(PCR) and CER3 clonotypic primers are additional methods, but are less often used.
The immunophenotype profile consists of CD5+ (in about 80%), CD10-/+,It is usually CD5
CD5 (protein)
CD5 is a cluster of differentiation found on a subset of IgM-secreting B cells called B-1 cells, and also on T cells. B-1 cells have limited diversity of their B-cell receptor due to their lack of the enzyme terminal deoxynucleotidyl transferase and are potentially self-reactive...
+ and CD10-. CD20+, CD23-/+ (though plus in rare cases). Generally, cyclin D1 is expressed but it may not be required. The workup for Mantle cell lymphoma is similar to the workup for many indolent lymphomas and certain aggressive lymphomas.
Mantle cell lymphoma is a systemic disease with frequent involvement of the bone marrow and gastrointestinal tract (generally showing polyposis in the lining). There is also a not-uncommon leukemic phase, marked by presence in the blood. For this reason, both the peripheral blood and bone marrow are evaluated for the presence of malignant cells. Chest, abdominal, and pelvic CT scans are routinely performed.
Since mantle cell lymphoma may present a lymphomatous polyposis coli and colon involvement is common, colonoscopy is now considered a routine part of the evaluation. Upper endoscopy and neck CT scan may be helpful in selected cases. In some patients with the blastic variant, lumbar puncture is done to evaluate the spinal fluid for involvement.
Causes
Attempts to determine causes of MCL have failed. It is not known what causes the translocation damage to the gene. Exposure to toxins is often mentioned as a possibility. The translocation damage to a gene is required in only one cell for the cancer to begin.Prognosis
The overall 5-year survival rate for MCL is generally 50% (advanced stage MCL) to 70% (for limited-stage MCL).Prognosis for individuals with MCL is problematic and indexes do not work as well due to patients presenting with advanced stage disease. Staging is used but is not very informative, since the malignant B-cells can travel freely though the lymphatic system and therefore most patients are at stage III or IV at diagnosis. Prognosis is not strongly affected by staging in MCL and the concept of metastasis does not really apply.
The Mantle Cell Lymphoma International Prognostic Index (MIPI) was derived from a data set of 455 advanced stage MCL patients treated in series of clinical trials in Germany/Europe. Of the evaluable population, approximately 18% were treated with high-dose therapy and stem cell transplantation in first remission. The MIPI is able to classify patients into three risk groups: low risk (median survival not reached after median 32 mos follow-up and 5-year OS rate of 60%), intermediate risk (median survival 51 months) and high risk (median survival 29 months). In addition to the 4 independent prognostic factors included in the model, the cell proliferation index (Ki-67) was also shown to have additional prognostic relevance. When the Ki67 is available, a biologic MIPI can be calculated.
(The letter A after the Roman numeral indicates that normal external symptoms are not present. The Letter B indicates the symptoms are present and hence they are called “B Symptoms”.)
MCL is one of the few NHLs that can cross the boundary into the brain, yet it can be treated in that event.
There are a number of prognostic indicators that have been studied. There is not universal agreement on their importance or usefulness in prognosis.
Ki-67
Ki-67 (Biology)
Antigen KI-67 also known as Ki-67 or MKI67 is a protein that in humans is encoded by the MKI67 gene .- Function :...
is an indicator of how fast cells mature and is expressed in a range from about 10% to 90%. The lower the percentage, the lower the speed of maturity, and the more indolent the disease. Katzenberger et al. Blood 2006;107:3407 graphs survival versus time for subsets of patients with varying Ki-67 indices. He shows median survival times of about one year for 61-90% Ki-67 and nearly 4 years for 5-20% Ki-67 index.
MCL cell types can aid in prognosis in a subjective way. Blastic is a larger cell type. Diffuse is spread through the node. Nodular are small groups of collected cells spread through the node. Diffuse and nodular are similar in behavior. Blastic is faster growing and it is harder to get long remissions. Some thought is that given a long time, some non-blastic MCL transforms to blastic. Although survival of most blastic patients is shorter, some data shows that 25% of blastic MCL patients survive to 5 years. That is longer than diffuse type and almost as long as nodular (almost 7 yrs).
Beta-2 microglobulin
Beta-2 microglobulin
β2 microglobulin also known as B2M is a component of MHC class I molecules, which are present on all nucleated cells . In humans, the β2 microglobulin protein is encoded by the B2M gene.-Structure and function:...
is another risk factor in MCL used primarily for transplant patients. Values less than 3 have yielded 95% overall survival to 6 yrs for auto SCT where over 3 yields a median of 44 mos overall survival for auto SCT (Khouri 03). This is not yet fully validated.
Testing for high levels of LDH
Lactate dehydrogenase
Lactate dehydrogenase is an enzyme present in a wide variety of organisms, including plants and animals.Lactate dehydrogenases exist in four distinct enzyme classes. Two of them are cytochrome c-dependent enzymes, each acting on either D-lactate or L-lactate...
in NHL patients is useful because LDH is released when body tissues break down for any reason. While it cannot be used as a sole means of diagnosing NHL, it is a surrogate for tracking tumor burden in those diagnosed by other means. The normal range is approximately 100-190.
Key diagnostics for MCL
- CT Scan - Computerized tomography scan yields images of part or whole body. Gives a large number of slices on X-ray image.
- PET Scan - Generally of the whole body, shows a three-dimensional image of where previously injected radioactive glucose is metabolized at a rapid rate. Faster-than-average metabolism shows as a black area and indicates that cancer is likely present. Metabolism of radioactive glucose may give a false positive, particularly if the patient has exercised before the test.
PET scans are much more effective when the information from them is integrated with that from a CT scan to show more precisely where the cancer activity is located and to more accurately measure the size of tumors.
Treatments
There are no proven standards of treatment for MCL, and there is no consensus among specialists on how to treat it optimally. Many regimens are available and often get good response rates, but patients almost always get disease progression after chemotherapy. Each relapse is typically more difficult to treat, and relapse is generally faster. Fortunately, regimens are available that will treat relapse, and new approaches are under test. Because of the aforementioned factors, many MCL patients enroll in clinical trials to get the latest treatments.There are four classes of treatments currently in general use: chemotherapy, immune based therapy, radioimmunotherapy and new biologic agents. The phases of treatment are generally: frontline, following diagnosis, consolidation, after frontline response (to prolong remissions), and relapse. Relapse is usually experienced multiple times.
Chemotherapy
ChemotherapyChemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
is widely used as frontline treatment, and often is not repeated in relapse due to side effects. Alternate chemotherapy is sometimes used at first relapse. For frontline treatment, CHOP
CHOP
CHOP is the acronym for a chemotherapy regimen used in the treatment of non-Hodgkin lymphoma. CHOP consists of:* Cyclophosphamide, an alkylating agent which damages DNA by binding to it and causing cross-links...
with rituximab
Rituximab
Rituximab, sold under the trade names Rituxan and MabThera, is a chimeric monoclonal antibody against the protein CD20, which is primarily found on the surface of B cells...
(Rituxan, Mabthera) is the most common chemotherapy, and often given as outpatient by IV. A stronger chemotherapy with greater side effects (mostly hematologic) is HyperCVAD
HyperCVAD
HyperCVAD is a chemotherapy regimen used to treat some forms of leukemia, non-Hodgkin lymphoma and lymphoblastic lymphoma.-Summary:...
, often given as in-patient, with rituximab and generally to fitter patients (some of which are over 65). HyperCVAD is becoming popular and showing promising results, especially with rituximab. It can be used on some elderly (over 65) patients, but seems only beneficial when the baseline Beta-2-MG blood test was normal. It is showing better complete remissions (CR) and progression free survival (PFS) than CHOP regimens. Another chemotherapy class is fludarabine
Fludarabine
Fludarabine or fludarabine phosphate is a chemotherapy drug used in the treatment of hematological malignancies. It has been unofficially and casually referred to as "AIDS in a bottle" amongst healthcare professionals due to its significant immunosuppresive activity.-Indications:Fludarabine is...
monotherapy, sometimes combined with cyclophosphamide and mitoxantrone, usually with rituximab. Cladribine
Cladribine
Cladribine is a drug used to treat hairy cell leukemia and multiple sclerosis. Its chemical name is 2-chlorodeoxyadenosine ....
and clofarabine
Clofarabine
Clofarabine is a purine nucleoside antimetabolite marketed in the U.S. and Canada as Clolar. In Europe and Australia/New Zealand the product is marketed under the name Evoltra. It is FDA-approved for treating a type of leukaemia called relapsed or refractory acute lymphoblastic leukaemia in...
are two other drugs being investigated in MCL. Cytotoxic chemotherapies, including bendamustin, are being studied alone and with similar combinations. A relatively new regimen that uses old drugs is PEP-C, which includes relatively small, daily doses of prednisone
Prednisone
Prednisone is a synthetic corticosteroid drug that is particularly effective as an immunosuppressant drug. It is used to treat certain inflammatory diseases and some types of cancer, but has significant adverse effects...
, etoposide
Etoposide
Etoposide phosphate is an anti-cancer agent. It is known in the laboratory as a topoisomerase poison. Etoposide is often incorrectly referred to as a topoisomerase inhibitor in order to avoid using the term "poison" in a clinical setting...
, procarbazine
Procarbazine
Procarbazine Procarbazine Procarbazine (Matulane (US), Natulan (Canada), Indicarb (India) is an antineoplastic chemotherapy drug for the treatment of Hodgkin's lymphoma and certain brain cancers (such as Glioblastoma multiforme). It is a member of a group of medicines called alkylating agents. It...
, and cyclophosphamide
Cyclophosphamide
Cyclophosphamide , also known as cytophosphane, is a nitrogen mustard alkylating agent, from the oxazophorines group....
, taken orally, has proven effective for relapsed patients. According to John Leonard M.D., a key researcher/proponent of PEP-C, may have anti-angiogenetic properties, something that he and his colleagues are testing through an ongoing drug trial.
Another approach involves using very high doses of chemotherapy, sometimes combined with total body irradiation
Total body irradiation
Total body irradiation is a form of radiotherapy used primarily as part of the preparative regimen for haematopoietic stem cell transplantation. As the name implies, TBI involves irradiation of the entire body, though in modern practice the lungs are often partially shielded to lower the risk of...
(TBI), in an attempt to destroy all evidence of the disease. The downside to this is the destruction of the patients' entire immune system as well, requiring rescue by transplantation of a new immune system (Hematopoietic stem cell transplantation), using either ones' own previously treated and stored stem cells (an autologous stem cell transplant), or those from a matched donor (an allogeneic stem cell transplant). A presentation at the December 2007 American Society of Hematology (ASH) conference by Christian Geisler, chairman of the Nordic Lymphoma Group (Copenhagen, Denmark), claimed that according to trial results, mantle cell lymphoma is potentially curable with very intensive chemo-immunotherapy followed by a stem cell transplant, when treated upon first presentation of the disease.
Immunotherapy
Immune-based therapyImmunotherapy
Immunotherapy is a medical term defined as the "treatment of disease by inducing, enhancing, or suppressing an immune response". Immunotherapies designed to elicit or amplify an immune response are classified as activation immunotherapies. While immunotherapies that reduce or suppress are...
is dominated now by the oft used and effective rituximab
Rituximab
Rituximab, sold under the trade names Rituxan and MabThera, is a chimeric monoclonal antibody against the protein CD20, which is primarily found on the surface of B cells...
monoclonal antibody, sold under the trade name Rituxan (or as Mabthera in Europe and Australia). Some say it is a landmark in medicine . Rituximab can have good activity against MCL alone but especially in combination with chemotherapies to prolong response duration. Rituximab essentially tags the cancer cells for destruction by the body. There are newer variations on monoclonal antibodies combined with radioactive molecules known as Radioimmunotherapy
Radioimmunotherapy
Radioimmunotherapy uses an antibody labeled with a radionuclide to deliver cytotoxic radiation to a target cell. In cancer therapy, an antibody with specificity for a tumor-associated antigen is used to deliver a lethal dose of radiation to the tumor cells...
(RIT). These include Zevalin and Bexxar. Rituximab has also been used in small numbers of patients in combination with thalidomide
Thalidomide
Thalidomide was introduced as a sedative drug in the late 1950s that was typically used to cure morning sickness. In 1961, it was withdrawn due to teratogenicity and neuropathy. There is now a growing clinical interest in thalidomide, and it is introduced as an immunomodulatory agent used...
with some effect.
It will be fruitful to investigate the use of Bexxar as first line treatment. This treatment appears to be less tiring for patients, since it consists of two injections at a distance of a week, while most other treatments consist of 6-8 cycles of chemotherapy combined with Rituximab.
In contrast to these antibody-based 'passive' immunotherapies, the field of 'active' immunotherapy tries to reprogram a patient's immune system to specifically recognize and eliminate their own tumor cells. Examples of active immunotherapy include cancer vaccine
Cancer vaccine
The term cancer vaccine refers to a vaccine that either prevents infections with cancer-causing viruses, treats existing cancer or prevents the development of cancer in certain high risk individuals...
s, adoptive cell transfer
Adoptive cell transfer
Adoptive cell transfer is the passive transfer of cells, most commonly immune-derived cells, into a new recipient host with the goal of transferring the immunologic functionality and characteristics into the new host...
, and immunotransplant
Immunotransplant
Immunotransplant is a maneuver used to make vaccines more powerful. It refers to the process of infusing vaccine-primed T lymphocytes into lymphodepleted recipients for the purpose of enhancing the proliferation and function of those T cells and increasing immune protection induced by that...
, which combines vaccination and autologous stem cell transplant. Though no active immunotherapies are currently a standard of care, numerous clinical trial
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
s are ongoing.
Targeted therapy
New targeted agents include the proteasome inhibitor Velcade and mTor inhibitors such as temsirolimus.Epidemiology
Of all cancers involving the same class of blood cellLymphoproliferative disorders
Lymphoproliferative disorders refer to several conditions in which lymphocytes are produced in excessive quantities. They typically occur in patients who have compromised immune systems...
, 6% of cases are mantle cell lymphoma.
External links
- A Brief Review of the Biology and Pathophysiology of Mantle Cell Lymphoma
- Mantle Cell Lymphoma Consortium
- Oral combination chemotherapy with Pep-C (C3) for mantle cell lymphoma (MCL): Daily prednisone, etoposide, procarbazine and cyclophosphamide. ASCO, 2003
- Oral combination chemotherapy for refractory/relapsed lymphoma with the PEP-C (C3) regimen (daily prednisone, etoposide, procarbazine, cyclophosphamide): Low-dose continuous metronomic multidrug therapy. 2007 ASCO Annual Meeting
- Lymphoma Association – Specialist UK charity providing free information and support to patients, their families, friends and carers
MultiMedia
- CME on MCL by Andre Goy, MD
- archived audiocasts at Leukemia & Lymphoma Society