AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Mantle cell lymphoma (MCL) is recognized in the Revised European-American Lymphoma and World Health Organization classifications as a distinct clinicopathologic entity. MCL was not recognized by previous lymphoma classification schemes; it was frequently categorized as diffuse small-cleaved cell lymphoma (by the International Working Formulation) or centrocytic lymphoma (by the Kiel classification). In the International Lymphoma Classification Project, it accounted for 8% of all non-Hodgkin lymphomas (NHLs).

Pathophysiology

MCL is a lymphoproliferative disorder derived from a subset of naive pregerminal center cells localized in primary follicles or in the mantle region of secondary follicles. Most cases of MCL are associated with chromosome translocation t(11;14)(q13;q32). This translocation involves the immunoglobulin heavy-chain gene on chromosome 14 and the BCL1 locus on chromosome 11. The molecular consequence of translocation is overexpression of the protein cyclin D1 (coded by the PRAD1 gene located close to the breakpoint). Cyclin D1 plays a key role in cell cycle regulation and progression of cells from G1 phase to S phase by activation of cyclin-dependent kinases.

Frequency

United States

NHL represents approximately 4% of all cancer diagnoses and is the seventh most common cancer. MCL represents 2-10% of all NHLs. In 1999, more than 55,000 new cases of NHL were diagnosed. The incidence of NHL of all types has increased by approximately 40% over the last 20 years, although the cause for this increase is unknown.

International

NHLs are 5 times more common than Hodgkin disease, representing approximately 4% of all cancers diagnosed internationally. The exact international prevalence of MCL is difficult to estimate because of the lack of uniform classification and procedures used for diagnosis.

Mortality/Morbidity

MCL is associated with a poor prognosis. Although MCL represents only 6% of NHLs, it remains incurable with current chemotherapeutic approaches. Despite response rates of 50-70% with many regimens, the disease typically progresses after chemotherapy. The median survival time is approximately 3 years (range, 2-5 y); the 10-year survival rate is only 5-10%.

• Developing reliable prognostic markers has been difficult in the absence of better-standardized therapy.


• The blastoid variant, commonly associated with TP53 mutations, has been associated with a worse prognosis. Gene expression profile analysis identified MCL patient subsets with more than 5 years' difference in median survival, based on cyclin D1 and other proliferation signature genes.

Race

Overall, whites are at higher risk for developing NHLs than blacks and Asian Americans.

Sex

The male-to-female ratio is 4:1.

Age

The age range at presentation is 35-85 years. Median age is 60 years.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Stage IV disease in 70% of patients
• B symptoms, which include fever, night sweats, and weight loss, in 40% of patients
• Generalized lymphadenopathy
• Abdominal distension from hepatosplenomegaly
• Fatigue from anemia or bulky disease
• Less common symptoms caused by extranodal involvement of GI tract, lungs, and CNS

Physical

• Generalized lymphadenopathy in 90%
• Splenomegaly in 60% (may be massive)
• Hepatomegaly in 30%
• Poor performance status in 20%
• Less commonly, palpable masses in skin, breast, and salivary glands

Causes

• No causative factor has been identified for MCL or for most patients with NHL of other types.
• NHL has been associated with viral infection (Ebstein-Barr virus, HIV, human T-lymphotropic virus type 1, human herpesvirus 6), environmental factors (pesticides, hair dyes), and primary and secondary immunodeficiency.
• Nonrandom chromosomal and molecular rearrangements play a major role in the pathogenesis of many lymphomas. The association of t(11;14)(q13;q32) with MCL suggests a causative role.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Follicular center cell lymphoma
Lymphoplasmacytic lymphoma
Marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type
Nonneoplastic hyperplasias (Castleman disease, mantle zone hyperplasia, reactive follicular hyperplasia)
Small lymphocytic lymphoma

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• CBC count
• • Anemia and cytopenias are secondary to bone marrow infiltration.
  • Lymphocytosis of more than 4000/µL occurs in 20-40% of cases.

• Chemistry
• • Patients have elevated lactate dehydrogenase levels, which correlate with tumor burden.
  • Patients have abnormal liver function test results from liver involvement.

• Beta2-microglobulin: The level may be elevated, which indicates a poor prognosis.
• Rare findings: These include hypogammaglobulinemia, monoclonal gammopathy, and a positive Coombs test result.

Imaging Studies

• Body CT scan: This study is important for initial staging and for assessing the patient's response to treatment.

Other Tests

• Immunocytochemistry
• • Tumor cells are monoclonal B cells that express surface immunoglobulin, immunoglobulin M, or immunoglobulin D.
  • Cells are characteristically CD5⁺ and pan B-cell antigen positive (eg, CD19, CD20, CD22) but lack expression of CD10 and CD23. Cyclin D1 is overexpressed.
  • Immunophenotyping helps differentiate MCL from other small B-cell lymphomas (see Table).

    Differential Diagnosis of MCL by Immunophenotyping

    Disease	CD5	CD20	CD23	CD10	CD103	FMC7	Cyelin D1	Sig*
    MCL	+	++	–	–	–	+/–	+	+
    B-CLL/SLL†	+	+	+	–	–	–	–	+
    PLL‡	–/+	++	+/–	–	–	+	–	++
    MZL§	–	++	–	–	–	+/–	–	+
    SLVL||	–	++	–/+	–	–	+/–	–	++
    LPL¶	–	+	–	–	–	–/+	–	++
    FL#	–	++	–	+	–	+/–	–	++
    HCL**	–	+	–	–	+	+	–/+	++

    *Surface immunoglobulins.
    ^†B-cell chronic lymphocytic leukemia/small lymphocytic leukemia.
    ^‡Prolymphocytic leukemia.
    ^§Marginal zone leukemia.
    ^||Splenic lymphoma with villous lymphocytes.
    ^¶Lymphoplasmacytic lymphoma.
    ^#Follicular lymphoma.
    **Hairy cell leukemia.

• Cytogenetics: Most cases of MCL are associated with a chromosome translocation between chromosome 11 and 14, t(11;14)(q13;q32).

Procedures

• Perform lymph node biopsy and aspiration together because aspiration alone is insufficient to establish a diagnosis.
• Use bone marrow aspirate/biopsy results for staging rather than diagnostic purposes.

Histologic Findings

Lymph node

Tumor is characterized by expansion of the mantle zone that surrounds the lymph node germinal centers by small-to-medium atypical lymphocytes. These cells have irregular and indented nuclei, moderately coarse chromatin, and scant cytoplasm, resembling smaller cells of follicular lymphoma. However, mitoses are more numerous and large cells are infrequent. A nodular appearance may be evident from expansion of the mantle zone in 30-50% of patients early in the disease. As disease progresses, the germinal centers become effaced, with obliteration of lymph node architecture.

A blastic variant of MCL, demonstrating numerous medium-to-large blastlike cells, has been reported and is associated with a more aggressive clinical course.

Bone marrow

In bone marrow sections, neoplastic cells may infiltrate in a focal, often paratrabecular or diffuse pattern. Diagnosis of MCL should not be based on the examination of bone marrow alone; obtaining a lymph node biopsy is required.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• MCL remains a difficult problem because of the lack of reliably curative treatments and the paucity of prospective clinical trials.
• Although 50-90% of these patients respond to combination chemotherapy, relatively few (30%) have a complete response. More aggressive chemotherapy regimens are currently under investigation and may yield higher complete response rates.
• An inexorable pattern of progression is characteristic, with a median time to treatment failure of less than 18 months. Median survival usually ranges from 2-5 years, and only 5-10% of patients survive 10 years.

Surgical Care

• Surgery, such as lymph node biopsy, is indicated for diagnosis.
• Albeit rarely, surgery may be indicated for therapeutic purposes, such as GI obstruction.

Consultations

• Hematologist
• Oncologist
• Surgeon - For lymph node biopsy, palliative procedures, and placement of a venous access device (eg, Port-a-Cath, Infus-a-Port) for chemotherapy administration

Diet

• Consultation with a dietitian may be necessary for patients with poor oral intake or marked weight loss.
• Special attention and support is required for patients receiving chemotherapy, such as appetite stimulants or diet supplements.
• Patients who are neutropenic require education about food hygiene.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Regimens for primary MCL therapy

Single alkylating agents

This therapy (eg, chlorambucil, 0.1-0.2 mg/kg for 3-6 wk) may be preferable for elderly patients or for those with serious comorbid medical problems who require therapy for lymphoma.

CVP and CHOP regimens

Combination chemotherapy (ie, cyclophosphamide, vincristine, prednisone [CVP]; cyclophosphamide, hydroxydaunomycin, Oncovin [vincristine], prednisone [CHOP]) was studied in a randomized prospective trial. The comparison of CVP and CHOP showed no advantage of adding doxorubicin, with similar response and survival rates. In some retrospective analyses, doxorubicin-containing regimens were associated with a longer event-free survival.

The dosages for CVP and CHOP chemotherapy regimens are as follows:

• CVP (administered every 21 d)
• • Cyclophosphamide at 400 mg/m²/d PO days 1-5 or 750-1000 mg/m² IV on day 1
  
  
  • Vincristine at 1.4 mg/m² IV on day 1, not to exceed 2 mg
  
  
  • Prednisone at 100 mg/m²/d PO on days 1-5


• CHOP (administered every 21 d)
• • Cyclophosphamide at 750 mg/² IV on day 1
  
  
  • Doxorubicin at 50 mg/² IV on day 1
  
  
  • Vincristine at 1.4 mg/² IV on day 1, not to exceed 2 mg
  
  
  • Prednisone at 100 mg/d PO on days 1-5

Hyper-CVAD (with or without rituximab) regimen

First-line therapy is with hyperfractionated cyclophosphamide, doxorubicin, vincristine, and dexamethasone (hyper-CVAD) with or without rituximab. Single-institution data (ie, M.D. Anderson Cancer Center) using hyper-CVAD plus rituximab yielded encouraging results as front-line therapy, especially in patients younger than 65 years.

Frontline therapy with hyper-CVAD plus rituximab (R-hyper-CVAD) in persons with MCL shows a higher complete response rate and response duration than any other regimen (100% response rate with 89% complete response). At 36 months, the failure-free survival rate was greater than 80% in patients younger than 65 years versus less than 50% in patients older than 65 years. In addition to age (ie, >65 y), beta2-microglobulin was found to be a very strong prognostic factor, especially in patients older than 65 years. Although very encouraging, this regimen is intensive and relatively toxic; data must be confirmed in randomized trials.

The hyper-CVAD drug regimen is a total of 8 cycles, 4 cycles of course A and 4 cycles of course B. Each cycle is started upon hematological recovery, usually every 3 weeks.

Course A is as follows:

• Rituximab at 375 mg/m² on day 1 of each cycle


• Cyclophosphamide at 300 mg/m² IV over 3 hours every 12 hours for 6 doses on days 1, 2, and 3 (Mesna may be given as an uroprotectant at the same total dose as cyclophosphamide but given by continuous infusion starting with cyclophosphamide and ending 5 h after the last dose.)


• Methotrexate at 12 mg IT on day 2


• Doxorubicin at 40 mg/m² IV on day 4


• Vincristine at 2 mg IV on days 4 and 11


• Dexamethasone at 40 mg/d PO/IV on days 1-4 and 11-14


• Cytarabine at 70 mg IT on day 7

Course B is as follows:

• Rituximab at 375 mg/m² on day 1 of each cycle


• Methotrexate at 1000 mg/m² IV over 24 hours on day 1


• Leucovorin at 25 mg/m² IV, 24 hours after the completion of the methotrexate infusion, every 6 hours for 6 doses


• Sodium bicarbonate at 600 mg PO (starting day before methotrexate) 3 times day for 4 days


• Cytarabine at 3 mg/m² IV over 2 hours every 12 hours for 4 doses on days 2 and 3

Premedication and supportive measures are recommended in combination with the R-hyper-CVAD regimen. With high-dose methotrexate, give hydration with sodium bicarbonate for 48 hours. Prophylactic use of dexamethasone 0.1% (Pred Forte ophthalmic solution), 1-2 drops every 4 hours while the patient is awake, for 7 days (during high-dose cytarabine administration) helps prevent conjunctivitis. Antibiotic also prophylaxis may be given. Additionally, doses should be modified according to the protocol with which the patient is being treated.

R-CHOP regimen

Another regimen is CHOP plus rituximab (R-CHOP). A phase 2 randomized trial of CHOP versus R-CHOP in patients with previously untreated MCL was reported by the German Low-Grade Lymphoma Study Group at the 2004 American Society of Clinical Oncology meeting. The complete response rate was higher with R-CHOP (34% vs 7%; P = .00024). The time to treatment failure was also in favor of R-CHOP, but the time to progression showed no significant difference.

Hyper-CVAD with autologous stem cell transplantation

Hyper-CVAD with or without rituximab followed by autologous stem cell transplantation (ASCT) was tested at the M.D. Anderson Cancer Center as a frontline regimen. It did not appear superior to hyper-CVAD over time, especially after the addition of rituximab to hyper-CVAD.

Regimens for relapsed or refractory MCL

R-hyper-CVAD

This therapy is currently being tested in patients with relapsed MCL in whom fludarabine or CHOP failed, but the results are not yet available. However, based on the frontline data, this is an acceptable option in patients with relapse. Future combinations of R-hyper-CVAD with other biologicals or new agents are potentially promising options.

Hyper-CVAD with or without rituximab followed by ASCT

Studies have shown that ASCT either as frontline consolidation or in the context of relapse provides high response rates and may improve disease-free survival, although this therapy is still typically associated with a continuous pattern of relapse.

Nucleoside analogues and combinations

With the use of fludarabine, mitoxantrone, and dexamethasone (FND); fludarabine and cyclophosphamide (FC); and fludarabine, cyclophosphamide, mitoxantrone (FCM), all with or without rituximab, evidence has shown that fludarabine as a single agent has activity in MCL. A higher complete response rate and/or longer response duration has been suggested when used in combination with an alkylator (eg, FC), with an anthracycline (eg, FND or fludarabine plus idarubicin), or both (eg, FCM). Such combinations could be used in refractory or relapse settings, with comparable response rates and duration of response.

The addition of rituximab to all of these regimens is clearly beneficial. For example, with FCM in a series of 38 patients with relapsed MCL, the overall response rate was 65% with rituximab versus 33% without rituximab, and the complete response rate was 35% with rituximab versus 0% without rituximab.

Other nucleoside analogs have activity in MCL, such as 2-chlorodeoxyadenosine, which was also found to be superior in combination with mitoxantrone.

Salvage chemotherapy combinations (eg, R-ICE, ESHAP) followed by ASCT

Rituximab, ifosfamide, carboplatin, and etoposide (R-ICE) or etoposide, methylprednisolone (Solu-Medrol), high-dose cytosine arabinoside, and cisplatin (ESHAP) followed by ASCT has been used; however the role of ASCT consolidation after salvage therapy remains controversial and may benefit only a subset of patients with relapsed MCL. On the other hand, data for nonmyeloablative transplantation are very promising, with some long-term survivors, including patients in whom prior high-dose therapy had failed.

Bortezomib (Velcade)

Recent trials from the Memorial Sloan-Kettering Cancer Center, National Cancer Institute of Canada, and M.D. Anderson Cancer Center have shown promising results with bortezomib for MCL. Goy and O'Connor have established the therapeutic activity of bortezomib in relapsed and refractory MCL, and their work is now being extended and confirmed in multicenter trials in the US and Canada with single-agent bortezomib, bortezomib in combination with chemotherapy and/or rituximab, and as a component of front-line therapy for MCL and other lymphomas (Fisher RI, J Clin Oncol 2005; 23:657-8).

FDA has recently (12/06) approved Velcade for MCL in patients who have recieved at least one prior therapy. This approval was based on findings from the PINNACLE trial, a prospective, phase 2, multicenter, single arm, open-label study of 155 patients. Overall response rate was 31% with 8% CR. Median duration of response was 9.3 months in responding patients and 15.4 in patients with CR.

Velcade Regimen:

Velcade 1.3 mg/m² IV push twice per week (days 1, 4, 8, 11) followed by 10-day treatment free period (21 day cycle) for 8 cycles. Patients with stable disease or partial responses could receive up to 1 y; not to exceed maximum 17 cycles.

Radioimmunotherapy

Both iodine I 131–based tositumomab (Bexxar) and yttrium 90–based ibritumomab tiuxetan (Zevalin) have shown activity as single agents for salvage therapy in persons with MCL. Studies have reported responses with radioimmunotherapy (RIT) in MCL, including some complete responses that lasted more than 1 year. Additional ongoing studies are exploring combinations of RIT with chemotherapy for untreated or relapsed MCL. Strategies including RIT as part of high-dose therapy have shown encouraging results.

The use of RIT as part of a nonmyeloablative allotransplantation conditioning regimen is another promising strategy currently being tested in clinical trials.

Monoclonal antibodies

The anti-CD20 monoclonal antibody rituximab, used as a single agent, has activity in MCL, yielding a response rate of 35%, a complete response rate of 10-15%, and a median duration of response of approximately 1 year in rituximab-naive patients. The potential role of rituximab as a maintenance therapy for patients with MCL is not yet well defined. The benefit of rituximab has been confirmed in combination with all chemotherapy regimens tested.

Rituximab and thalidomide combination

Promising results have been shown using rituximab (standard dose) and thalidomide (200 mg/d, with incremental dose increases to 400 mg on day 15) continued as maintenance therapy until progression or relapse. In this small series, the response rate was 81% (complete response rate of 31%) and the median progression-free survival was 20.4 months (95% confidence interval, 17.3-23.6). The estimated 3-year survival rate was 75%. This approach would be an appealing alternative in elderly patients.

High-dose chemotherapy with autologous bone marrow or stem cell transplantation

High-dose chemotherapy with autologous bone marrow or stem cell transplantation has not been proven curative for MCL when used as second-line therapy. Long-term survival data are currently unavailable in the setting of high-dose chemotherapy applied as consolidation therapy to patients in first complete remission

New agents and combinations in trials:

1. Chemotherapy + Rituximab followed by RIT: this option is currently being tested as part of frontline therapy.

2. mTOR inhibitors 14, CDK inhibitors or small molecule inhibitors of Bcl-2 family members. However these compounds are still being tested as part of clinical trials. Preclinical data suggest that several of these new biological agents can be combined with rituximab showing additive or synergistic effect.

3. Combination of bortezomib and rituximab, which was tested in indolent NHL (follicular and marginal zone) 15 and is currently being tested in MCL as well.

4. Promising results have also been shown using rituximab (standard dose) and thalidomide 16 with an ORR of 81% (CR rate 31%) and median progression-free survival (PFS) was 20.4 months (95% CI, 17.3 to 23.6) in the relapse setting.

5. Lenalidomide - rituximab also being tested.

For selected patients, allogeneic hematopoietic stem cell transplantation from HLA-matched donors is a potential therapeutic option that remains investigational.

Drug Category: Alkylating agents

Impair cell function by forming covalent bonds with DNA, RNA, and proteins. Alkylating agents are not cell cycle phase–specific and are used for both hematologic and nonhematologic malignancies.

Drug Name	Cyclophosphamide (Cytoxan)
Description	Used mainly in combination regimens for hematologic and nonhematologic malignancies. Part of CHOP and CVP regimens for lymphoma treatment.
Adult Dose	750-1000 mg/m2 IV on day 1 in CHOP and CVP regimens
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; severely depressed bone marrow function; nursing mothers; serious infection
Interactions	Barbiturates may increase cyclophosphamide conversion to its toxic metabolites; chloramphenicol half-life is increased; succinylcholine metabolism is blocked; increases leukopenia with thiazide diuretics; anticoagulants effect increased; digoxin level decreased; doxorubicin-induced cardiotoxicity increased
Pregnancy	D - Unsafe in pregnancy
Precautions	Depressed bone marrow function, known hypersensitivity, and recent radiation therapy

Drug Category: Anthracycline antibiotics

Bind to nucleic acid by intercalation with base pairs of DNA double helix, interfering with DNA synthesis. Causes inhibition of DNA topoisomerases I and II.

Drug Category: Vinca alkaloids

Inhibit microtubule assembly, causing arrest of cell division at metaphase stage of mitosis. Cell cycle phase–specific at M and S phases.

Drug Category: Corticosteroids

Glucocorticoids cause profound and varied metabolic effects. In addition, modify immune responses to diverse stimuli.

Drug Category: Interferons

Mechanism by which exerts antitumor or antiviral activity not clearly understood. However, direct antiproliferative action against tumor cells, inhibition of virus replication, and modulation of host immune responses are believed to possibly play important roles.

Drug Category: Monoclonal antibodies

Rituximab is a genetically engineered chimeric (murine and human) monoclonal antibody directed against the CD20 antigen found on surface of normal cells and in high copy number on malignant B lymphocytes.

Drug Category: Proteasome inhibitor

Disrupts cell cycle and pathways supporting cell growth.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Admit patients for complications or disease progression.
• Admit patients for adverse chemotherapy effects, such as neutropenic fever or mucositis.

Further Outpatient Care

• Usually, treatment and follow-up care of patients with MCL is performed in an outpatient setting.
• Carefully monitor blood cell count prior to administering chemotherapy and 10-14 days after each treatment cycle.
• Evaluate disease by monitoring history, physical examination findings, and imaging study results.
• Monitor adverse effects of chemotherapy by monitoring history, physical examination findings, and CBC counts.
• Provide symptomatic treatment for adverse effects such as nausea, vomiting, diarrhea, mucositis, and fatigue.
• Provide psychosocial support.

Complications

• Complications from disease progression
• • Cytopenias (neutropenia, anemia, thrombocytopenia) secondary to bone marrow infiltration
  • GI, pulmonary, or CNS complications secondary to extranodal involvement
  • Leukocytosis (lymphocytosis) in the leukemic phase of disease

• Complications from chemotherapy
• • Infection, neutropenia, anemia, and thrombocytopenia
  • Fatigue
  • Neuropathy
  • Dehydration after diarrhea or vomiting
  • Cardiac toxicity from doxorubicin

Prognosis

• MCL exhibits a moderately aggressive course similar to that of intermediate-grade NHL. Unlike intermediate-grade lymphomas, it is rarely curable with currently available standard treatment.
• Median overall survival is 2-5 years. Younger age and limited disease are favorable prognostic features. Complete responses are rare with standard chemotherapy. Median time to treatment failure is less than 18 months.

Patient Education

• Clearly explain all available treatment options and provide detailed instruction about the adverse effects of chemotherapy. Consider enrollment of the patient into a clinical trial.
• Provide psychosocial counseling.
• For excellent patient education resources, visit eMedicine's Blood and Lymphatic System Center. Also, see eMedicine's patient education article Lymphoma.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to ensure that the patient understands this disease and the available treatment options prior to starting a treatment modality, such as chemotherapy
• Failure to discuss all risks (including, but not limited to, death) and benefits, answer questions, or obtain informed consent prior to initiating chemotherapy
• Failure to prevent medication errors (a common source of lawsuits)
• Failure to pay special attention while writing and administering chemotherapy, with chemotherapy checks at the pharmacy and nursing levels prior to administration

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Assouline S, Belch A, Sehn L, et al. A phase II study of bortezomib in patients with mantle cell lymphoma. Poster session 578-III. National Cancer Institute of Canada Clinical Trials Group. Kingston, Ontario, Canada.
• Campo E, Raffeld M, Jaffe ES. Mantle-cell lymphoma: New treatment possibilities. Semin Hematol. Apr 1999;36(2):115-27. [Medline].
• Cohen BJ, Moskowitz C, Straus D, et al. Cyclophosphamide/fludarabine (CF) is active in the treatment of mantle cell lymphoma. Leuk Lymphoma. Sep-Oct 2001;42(5):1015-22. [Medline].
• Coiffier B. Mantle Cell Lymphoma: New treatment possibilities. In: American Society of Hematology Education Program Book. Miami, Fla:. American Society of Hematology;1999:329-34.
• Coiffier B. Which treatment for mantle-cell lymphoma patients in 1998?. J Clin Oncol. Jan 1998;16(1):3-5. [Medline].
• Dreger P, Martin S, Kuse R, et al. The impact of autologous stem cell transplantation on the prognosis of mantle cell lymphoma: a joint analysis of two prospective studies with 46 patients. Hematol J. 2000;1(2):87-94. [Medline].
• Fisher RI. Mantle Cell Lymphoma: Prognostic factors and Treatment results. In: American Society of Hematology Education Program Book. Miami, Fla:. American Society of Hematology;1999:325-8.
• Fisher RI, Dahlberg S, Nathwani BN, et al. A clinical analysis of two indolent lymphoma entities: mantle cell lymphoma and marginal zone lymphoma (including the mucosa-associated lymphoid tissue and monocytoid B-cell subcategories): a Southwest Oncology Group study. Blood. Feb 15 1995;85(4):1075-82. [Medline].
• Foran JM, Rohatiner AZ, Cunningham D, et al. European phase II study of rituximab (chimeric anti-CD20 monoclonal antibody) for patients with newly diagnosed mantle-cell lymphoma and previously treated mantle-cell lymphoma, immunocytoma, and small B-cell lymphocytic lymphoma. J Clin Oncol. Jan 2000;18(2):317-24. [Medline].
• Freedman AS, Neuberg D, Gribben JG, et al. High-dose chemoradiotherapy and anti-B-cell monoclonal antibody-purged autologous bone marrow transplantation in mantle-cell lymphoma: no evidence for long-term remission. J Clin Oncol. Jan 1998;16(1):13-8. [Medline].
• Goy A, Younes A, McLaughlin P, et al. Update on a phase (ph) 2 study of bortezomib in patients (pts) with relapsed or refractory indolent or aggressive non-Hodgkin’s lymphomas (NHL). ASCO Annual Meeting Proceedings (Post-Meeting Edition). J Clin Oncol. 2004;22 (July 15 suppl):14S (6581).
• Harris NL, Jaffe ES, Diebold J, et al. The World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues. Report of the Clinical Advisory Committee meeting, Airlie House, Virginia, November, 1997. - Bloomfield CD. Dec 1999;10(12):1419-32. [Medline].
• Harris NL, Jaffe ES, Stein H, et al. A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood. Sep 1 1994;84(5):1361-92. [Medline].
• Hiddemann W, Dreyling M, Unterhalt M, et al. Rituximab plus chemotherapy in follicular and mantle cell lymphomas. Semin Oncol. Feb 2003;30(1 Suppl 2):16-20. [Medline].
• Jaffe ES, Campo E, Raffeild M. Mantle Cell Lymphoma: Biology and Diagnosis. In: American Society of Hematology Education Program Book. Miami, Fla:. American Society of Hematology;1999:319-24.
• Kaufmann H, Raderer M, Wöhrer S. Antitumor activity of rituximab plus thalidomide in patients with relapsed/refractory mantle cell lymphoma. Blood. Oct 15 2004;104(8):2269-71. [Medline].
• Khouri IF, Saliba RM, Okoroji GJ, et al. Long-term follow-up of autologous stem cell transplantation in patients with diffuse mantle cell lymphoma in first disease remission: the prognostic value of beta2-microglobulin and the tumor score. Cancer. Dec 15 2003;98(12):2630-5. [Medline].
• Khouri IF, Lee MS, Saliba RM, et al. Nonablative allogeneic stem-cell transplantation for advanced/recurrent mantle-cell lymphoma. J Clin Oncol. Dec 1 2003;21(23):4407-12. [Medline].
• Lefrère F, Delmer A, Suzan F, et al. Sequential chemotherapy by CHOP and DHAP regimens followed by high-dose therapy with stem cell transplantation induces a high rate of complete response and improves event-free survival in mantle cell lymphoma: a prospective study. Leukemia. Apr 2002;16(4):587-93. [Medline].
• O'Connor OA. Marked clinical activity of the novel proteasome inhibitor bortezomib in patients with relapsed follicular (RL) and mantle cell lymphoma (MCL). ASCO Annual Meeting Proceedings (Post-Meeting Edition). J Clin Oncol. 2004;22 (July 15 suppl):14S (6582).
• Rosenwald A, Wright G, Wiestner A, et al. The proliferation gene expression signature is a quantitative integrator of oncogenic events that predicts survival in mantle cell lymphoma. Cancer Cell. Feb 2003;3(2):185-97. [Medline].
• Seng JE, Peterson BA. Indolent B-cell non-Hodgkin's lymphomas. Oncology (Huntingt). Dec 1997;11(12):1883-94, 1987; discussion 1901-2, 1. [Medline].
• Ship MA, Mauch PM, Nancy LH. Non-Hodgkin's Lymphoma. In: Cancer: Principles & Practice of Oncology. 5th ed. Philadelphia, Pa:. Lippencott, Williams & Wilkins;1997.
• The Non-Hodgkin's Lymphoma Pathologic Classification Project. National Cancer Institute sponsored study of classifications of non- Hodgkin's lymphomas: summary and description of a working formulation for clinical usage. Cancer. May 15 1982;49(10):2112-35. [Medline].
• Vose JM, Bierman PJ, Lynch JC. Long Term Results of Radioimmunotherapy with Bexxar/BEAM and Autologous Stem Cell Transplantation (ASCT) for Chemotherapy Resistant Aggressive Non-Hodgkin s Lymphoma (NHL). Oral Session. University of Nebraska Medical Center. Omaha, Nebraska.
• Weisenburger DD, Armitage JO. Mantle cell lymphoma-- an entity comes of age. Blood. Jun 1 1996;87(11):4483-94. [Medline].
• Witzig TE, White CA, Wiseman GA, et al. Phase I/II trial of IDEC-Y2B8 radioimmunotherapy for treatment of relapsed or refractory CD20(+) B-cell non-Hodgkin's lymphoma. J Clin Oncol. Dec 1999;17(12):3793-803. [Medline].
• Younes A, Pro B, Delpassand E. A phase II study of 90-yttrium-ibritumomab (Zevalin) for the treatment of patients with relapsed and refractory mantle cell lymphoma (MCL). Poster session 588-I. M.D. Anderson Cancer Center. Houston, Texas.
• Zinzani PL, Magagnoli M, Moretti L, et al. Randomized trial of fludarabine versus fludarabine and idarubicin as frontline treatment in patients with indolent or mantle-cell lymphoma. J Clin Oncol. Feb 2000;18(4):773-9. [Medline].

Article Last Updated: May 14, 2007