What is the role of chemotherapy in the treatment of Burkitt lymphoma/Burkitt-like lymphoma (BL/BLL)?

Answer

Intensive systemic chemotherapy is the treatment of choice for this aggressive disease in all its stages.^[33]All clinical variants of Burkitt lymphoma are treated generally the same. The overall survival rate associated with Burkitt lymphoma depends upon the stage of the disease at initial diagnosis. Patients with localized disease respond well to chemotherapy and have an excellent survival rate. Patients with disseminated disease respond less well to chemotherapy and have a less favorable survival rate. Increasing age has also been associated with inferior outcome in most clinical trials.^{[6, 54]}(See Staging and Prognosis.)

For patients who refuse, or are not candidates for clinical trials, short-duration, intensive, alkylator-based, multiagent chemotherapy regimens with adequate central nervous system (CNS) prophylaxis are necessary. Administration of less intensive chemotherapy regimens used in other non-Hodgkin lymphomas (NHL) (eg, CHOP [cyclophosphamide, hydroxydaunorubicin hydrochloride (doxorubicin hydrochloride), vincristine and prednisone]) usually results in frequent relapses and inferior survival. Of particular importance is the rapid administration of successive cycles of intensive multidrug therapy to prevent tumor regrowth. Dose reduction should also be avoided if possible.^[55]

Most adult Burkitt lymphoma regimens were initially adopted from the pediatric study protocols that used several known active agents, including cyclophosphamide, vincristine, methotrexate, doxorubicin, and cytarabine. The French (LMB 81, 84, 86, and 89) and the German (B-NHL 83, B-NHL 86) protocols as well as the CODOX-M/IVAC regimen (cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate / ifosfamide, etoposide, high-dose cytarabine) were modified and used in adult patients with acceptable outcomes (2-y overall survival: 40-74%). Other protocols (hyper-CVAD [modified fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone], Cancer and Leukemia Group B [CALGB] 9251, etc) were evaluated primarily in adults.

A study by Todeschini et al found that intensive pediatric-based chemotherapy regimen increased remission and survival rates in both children and adults with Burtkitt lymphoma.^[56]

Even though a standard regimen is not available yet, in general, three treatment approaches are available:

Intensive, short-duration regimens like CODOX-M/IVAC (Magrath regimen) and the CALGB 9251 protocol
Long-duration chemotherapy similar to acute lymphoblastic leukemia (ALL) treatment, like hyper-CVAD and the CALGB 8811 protocol
Combination regimens followed by autologous stem cell transplantation (SCT)
Most current regimens have added rituximab to previously established chemotherapy regimens

Despite the fact that no direct comparison has been done among these different approaches, the short-duration, more intense regimens are usually preferred in most US institutions, because they are faster to administer (ALL-type treatment may take up to 2 y and usually involves a maintenance arm) and less complicated than ALL-type treatment or SCT. The regimen most frequently used is CODOX-M/IVAC.

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Media Gallery

Computed tomography scan in a patient with a large, left-sided axillary mass from which a biopsy was obtained. Biopsy findings were consistent with small noncleaved cell non-Hodgkin lymphoma.
Postchemotherapy computed tomography scan in a patient diagnosed with small noncleaved cell lymphoma (SNCCL) (same patient as in previous image). This image shows regression of a left axillary mass.
Coronal magnetic resonance imaging (MRI) section in a patient with large neck mass (same patient as in previous image). Biopsy findings showed Burkitt-like non-Hodgkin lymphoma (NHL). MRI was performed to assess for cord involvement.
Sagittal magnetic resonance imaging (MRI) section of the neck area showing a large mass invading the cervical spine with epidural encroachment (same patient as in the previous image). MRI was performed to rule out cord compression. The first image shows the gallium scan of this patient that correlates with the site of the tumor.
Right-sided pleural effusion in a patient with small noncleaved cell lymphoma (SNCCL) non-Hodgkin lymphoma.
Hematoxylin and eosin (H&E) stain. Sheets of monotonous-appearing lymphoid cells with one or more prominent nucleoli and an area of pale staining resulting from the presence of benign macrophages reveal a starry sky pattern.
The 2-dimensional flow cytometry demonstrates the highlighted cells to be CD5 negative and CD23 negative as well as lambda negative. Small noncleaved cell lymphoma (SNCCL) cells are typically CD19+, CD20+, CD22+, and CD10+.

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Author

Ali H Kanbar, MD Medical Oncologist/Hematologist, Dayton Cancer Center

Ali H Kanbar, MD is a member of the following medical societies: American College of Physicians, American Society of Hematology, American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Coauthor(s)

Ronald A Sacher, MBBCh, FRCPC, DTM&H Professor of Internal Medicine and Pathology, Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center

Ronald A Sacher, MBBCh, FRCPC, DTM&H is a member of the following medical societies: American Association for the Advancement of Science, American Association of Blood Banks, American Clinical and Climatological Association, American Society for Clinical Pathology, American Society of Hematology, College of American Pathologists, International Society of Blood Transfusion, International Society on Thrombosis and Haemostasis, Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Acknowledgements

Patturajah Anbumani, MD, MBBS, MS, MCh Associate Medical Director, Best Medical Care; Former Associate Medical Director, Jeanes Hospital, Temple University Health System; Former Adjunct Clinical Assistant Professor, New York College of Osteopathic Medicine; Former Clinical Assistant Professor, Department of Medicine, State University of New York-Downstate

Patturajah Anbumani, MD, MBBS, MS, MCh is a member of the following medical societies: American College of Physicians, American Medical Association, and American Medical Women’s Association

Disclosure: Nothing to disclose.

Samer A Bleibel, MD Staff Physician, Department of Internal Medicine, Wayne State University School of Medicine, St John's Hospital and Medical Centers

Samer A Bleibel, MD is a member of the following medical societies: American College of Physicians

Disclosure: Nothing to disclose.

Asher A Chanan-Khan, MD Assistant Professor, Department of Medicine, Division of Lymphoma and Bone Marrow Transplantation, Roswell Park Cancer Institute, State University of New York at Buffalo

Asher A Chanan-Khan, MD is a member of the following medical societies: American College of Physicians, American Medical Association, and American Society of Hematology

Disclosure: Nothing to disclose.

Hanxian Huang, MD, PhD Staff Physician, Department of Internal Medicine, Leesburg Regional Medical Center, The Villages Regional Hospital

Hanxian Huang, MD, PhD is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine

Disclosure: Nothing to disclose.

Anand B Karnad, MBBS Program Director, Fellowship Programs in Hematology-Oncology, Professor of Medicine, Division of Medical Oncology, Department of Medicine, University of Texas Health Sciences Center, San Antonio

Anand B Karnad, MBBS is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Osler Society, American Society of Hematology, Assocation of Subspecialty Professors, and Massachusetts Medical Society

Disclosure: Nothing to disclose.

Olga Kozyreva, MD Attending Physician, Division of Hematology-Oncology, St Elizabeth's Medical Center; Assistant Professor, Tufts University School of Medicine

Disclosure: Nothing to disclose.

Sarah K May, MD Consulting Staff, Department of Hematology-Oncology, Caritas Carney Hospital, Commonwealth Hematology-Oncology PC

Disclosure: Nothing to disclose.

from Memorial Sloan-Kettering - Philip Schulman, MD Chief, Medical Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center; Clinical Professor, Department of Medicine, New York University School of Medicine

Philip Schulman, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, American Society of Hematology, and Medical Society of the State of New York

Disclosure: Nothing to disclose.

Karen Seiter, MD Professor, Department of Internal Medicine, Division of Oncology/Hematology, New York Medical College

Karen Seiter, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, and American Society of Hematology

Disclosure: Novartis Honoraria Speaking and teaching; Schering Honoraria Speaking and teaching; Cephalon Honoraria Speaking and teaching; Celgene Honoraria Speaking and teaching

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

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Yubao Wang, MD, PhD Fellow, Division of Hematology/Medical Oncology, University of Texas Health Science Center, San Antonio

Yubao Wang, MD, PhD is a member of the following medical societies: American College of Physicians, American Society of Clinical Oncology, and American Society of Hematology

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