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Chronic lymphocytic leukemia


Table of Contents

GENERAL INFORMATION
STAGE INFORMATION
Rai Staging System
Stage 0
Stage I
Stage II
Stage III
Stage IV
Binet classification
TREATMENT OPTION OVERVIEW
STAGE 0 CHRONIC LYMPHOCYTIC LEUKEMIA
STAGE I CHRONIC LYMPHOCYTIC LEUKEMIA
STAGE II CHRONIC LYMPHOCYTIC LEUKEMIA
STAGE III CHRONIC LYMPHOCYTIC LEUKEMIA
STAGE IV CHRONIC LYMPHOCYTIC LEUKEMIA
REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA

GENERAL INFORMATION

Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. Refer to the PDQ levels of evidence summary for more information.

Chronic lymphocytic leukemia (CLL) is a disorder of morphologically mature but immunologically less mature lymphocytes and is manifested by progressive accumulation of these cells in the blood, bone marrow, and lymphatic tissues. Lymphocyte counts in the blood are usually equal to or higher than 10,000 per cubic millimeter.[1] There is no curative therapy. The overall 5-year survival is approximately 60%, but depends on stage of disease. Antileukemic therapy is frequently unnecessary in uncomplicated early disease.[2]

CLL occurs primarily in middle-aged and elderly individuals, with increasing frequency in successive decades of life.[3] The clinical course of this disease progresses from an indolent lymphocytosis without other evident disease to one of generalized lymphatic enlargement with concomitant pancytopenia. Complications of pancytopenia, including hemorrhage and infection, represent a major cause of death in these patients.[4] Immunological aberrations, including Coombs-positive hemolytic anemia, immune thrombocytopenia, and depressed immunoglobulin levels may all complicate the management of CLL.

Confusion with other diseases may be avoided by determination of cell surface markers. CLL lymphocytes coexpress the B-cell antigens CD19 and CD20 along with the T-cell antigen CD5.[5] This coexpression only occurs in one other disease entity, mantle cell lymphoma. CLL B cells express relatively low levels of surface-membrane immunoglobulin (compared with normal peripheral blood B cells) and a single light chain (kappa or lambda).[2] CLL is diagnosed by an absolute increase in lymphocytosis and/or bone marrow infiltration coupled with the characteristic features of morphology and immunophenotype.

The differential diagnosis must exclude hairy cell leukemia (a separate summary containing information on hairy cell leukemia is also available in PDQ), and Waldenstrom's macroglobulinemia (discussed in the PDQ summary containing information on plasma cell neoplasm). Waldenstrom's macroglobulinemia has a natural history and therapeutic options similar to CLL, with the exception of hyperviscosity syndrome associated with macroglobulinemia as a result of elevated immunoglobulin M. Prolymphocytic leukemia (PLL) is a rare entity characterized by excessive prolymphocytes in the blood with a typical phenotype that is positive for CD19, CD20, and surface-membrane immunoglobulin and negative for CD5. These patients demonstrate splenomegaly and poor response to low-dose or high-dose chemotherapy.[2,6] Cladribine (2-chlorodeoxyadenosine) appears to be an active agent (60% complete remission rate) for patients with de novo B-cell prolymphocytic leukemia.[7][Level of evidence: 3iiiDiii] Patients with CLL who show prolymphocytoid transformation maintain the classic CLL phenotype and have a worse prognosis than PLL patients. Large granular lymphocytic leukemia is characterized by lymphocytosis with a natural killer cell immunophenotype (CD2, CD16, and CD56) or a T-cell immunophenotype (CD2, CD3, and CD8).[8,9] These patients often have neutropenia and a history of rheumatoid arthritis. The natural history is indolent, often marked by anemia and splenomegaly. This condition appears to fit into the clinical spectrum of Felty's syndrome.[10] Therapy includes steroids, low doses of oral cyclophosphamide or methotrexate, and treatment of the bacterial infections acquired during severe neutropenia.[8,11,12]

References:

  1. International Workshop on Chronic Lymphocytic Leukemia: Chronic lymphocytic leukemia: recommendations for diagnosis, staging, and response criteria. Annals of Internal Medicine 110(3): 236-238, 1989.

  2. Rozman C, Montserrat E: Chronic lymphocytic leukemia. New England Journal of Medicine 333(16): 1052-1057, 1995.

  3. Catovsky D, Fooks J, Richards S: Prognostic factors in chronic lymphocytic leukaemia: the importance of age, sex and response to treatment in survival: a report from the MRC CLL 1 trial. British Journal of Haematology 72(2): 141-149, 1989.

  4. Anaissie EJ, Kontoyiannis DP, O'Brien S, et al.: Infections in patients with chronic lymphocytic leukemia treated with fludarabine. Annals of Internal Medicine 129(7): 559-566, 1998.

  5. DiGiuseppe JA, Borowitz MJ: Clinical utility of flow cytometry in the chronic lymphoid leukemias. Seminars in Oncology 25(1): 6-10, 1998.

  6. Melo JV, Catovsky D, Galton DA: The relationship between chronic lymphocytic leukaemia and prolymphocytic leukaemia: I. Clinical and laboratory features of 300 patients and characterization of an intermediate group. British Journal of Haematology 63: 377-387, 1986.

  7. Saven A, Lee T, Schlutz M, et al.: Major activity of cladribine in patients with de novo B-cell prolymphocytic leukemia. Journal of Clinical Oncology 15(1): 37-43, 1997.

  8. Loughran TP: Clonal diseases of large granular lymphocytes. Blood 82(1): 1-14, 1993.

  9. Semenzato G, Zambello R, Starkebaum G, et al.: The lymphoproliferative disease of granular lymphocytes: updated criteria for diagnosis. Blood 89(1): 256-260, 1997.

  10. Bowman SJ, Sivakumaran M, Snowden N, et al.: The large granular lymphocyte syndrome with rheumatoid arthritis: immunogenetic evidence for a broader definition of Felty's syndrome. Arthritis and Rheumatism 37(9): 1326-1330, 1994.

  11. Loughran TP, Kidd PG, Starkebaum G: Treatment of large granular lymphocyte leukemia with oral low-dose methotrexate. Blood 84(7): 2164-2170, 1994.

  12. Dhodapkar MV, Li CY, Lust JA, et al.: Clinical spectrum of clonal proliferations of T-large granular lymphocytes: a T-cell clonopathy of undetermined significance? Blood 84(5): 1620-1627, 1994.


STAGE INFORMATION

Staging is useful in this disease to predict prognosis and also to stratify patients to achieve comparability of interpreting specific treatment results. Anemia and thrombocytopenia are the major adverse prognostic variables.

Chronic lymphocytic leukemia (CLL) has no standard staging system. The Rai staging system and the Binet classification are presented below.[1,2] An NCI-sponsored working group has formulated standardized guidelines for eligibility, response, and toxic effects criteria to be used in future clinical trials in CLL.[3]


Rai Staging System


Stage 0

Stage 0 chronic lymphocytic leukemia: absolute lymphocytosis (>15,000 per cubic millimeter) without adenopathy, hepatosplenomegaly, anemia, or thrombocytopenia.


Stage I

Stage I chronic lymphocytic leukemia: absolute lymphocytosis with lymphadenopathy without hepatosplenomegaly, anemia, or thrombocytopenia.


Stage II

Stage II chronic lymphocytic leukemia: absolute lymphocytosis with either hepatomegaly or splenomegaly, with or without lymphadenopathy.


Stage III

Stage III chronic lymphocytic leukemia: absolute lymphocytosis and anemia (hemoglobin <11 g/dL) with or without lymphadenopathy, hepatomegaly, or splenomegaly.


Stage IV

Stage IV chronic lymphocytic leukemia: absolute lymphocytosis and thrombocytopenia (<100,000 per cubic millimeter) with or without lymphadenopathy, hepatomegaly, splenomegaly, or anemia.


Binet classification

Clinical stage A: no anemia or thrombocytopenia and fewer than three areas of

lymphoid involvement (Rai stages 0, I, and II)*

Clinical stage B: no anemia or thrombocytopenia with three or more areas of
lymphoid involvement (Rai stages I and II)*

Clinical stage C: anemia and/or thrombocytopenia regardless of the number of
areas of lymphoid enlargement (Rai stages III and IV)

*Lymphoid areas include cervical, axillary, inguinal, and spleen.

The Binet classification integrates the number of nodal groups involved with the disease with bone marrow failure. Its major benefit derives from the recognition of a predominantly splenic form of the disease, which may have a better prognosis than in the Rai staging, and from recognition that the presence of anemia or thrombocytopenia has a similar prognosis and does not merit a separate stage. Neither system separates immune from nonimmune causes of cytopenia. Patients with thrombocytopenia or anemia or both due to extensive marrow infiltration and impaired production (Rai III/IV, Binet C) have a poorer prognosis than patients with immune cytopenias.[4] The International Workshop on Chronic Lymphocytic Leukemia has recommended integrating the Rai and Binet systems as follows: A(0), A(I), A(II); B(I), B(II); and C(III), C(IV).[5] The National Cancer Institute-sponsored Working Group has published guidelines for the diagnosis and treatment of CLL in both clinical trial and general practice settings.[3] Use of these systems allows comparison of clinical results and establishment of therapeutic guidelines.

References:

  1. Rai KR, Sawitsky A, Cronkite EP, et al.: Clinical staging of chronic lymphocytic leukemia. Blood 46(2): 219-234, 1975.

  2. Binet JL, Auquier A, Dighiero G, et al.: A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis. Cancer 48(1): 198-206, 1981.

  3. Cheson BD, Bennett JM, Grever M, et al.: National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood 87(12): 4990-4997, 1996.

  4. Mandelli F, De Rossi G, Mancini P, et al: Prognosis in chronic lymphocytic leukemia: a retrospective multicentric study from the GIMEMA group. Journal of Clinical Oncology 5(3): 398-406, 1987.

  5. International Workshop on Chronic Lymphocytic Leukemia: Chronic lymphocytic leukemia: recommendations for diagnosis, staging, and response criteria. Annals of Internal Medicine 110(3): 236-238, 1989.


TREATMENT OPTION OVERVIEW

Treatment of chronic lymphocytic leukemia (CLL) ranges from periodic observation with treatment of infectious, hemorrhagic, or immunologic complications to a variety of experimental therapies. Because this disease is generally not curable, occurs in an elderly population, and often progresses slowly, it is generally treated in a conservative fashion.[1] A variety of clinical factors, including beta-2-microglobulin, lymphocyte doubling-time, and cytogenetic abnormalities, may be helpful in predicting progression of disease.[2]

Infectious complications in advanced disease are in part a consequence of the hypogammaglobulinemia and the inability to mount a humoral defense against bacterial or viral agents. Herpes zoster represents a frequent viral infection in these patients, but infections with Pneumocystis carinii and Candida albicans may also occur. The early recognition of infections and the institution of appropriate therapy are critical to the long-term survival of these patients. A randomized study of intravenous immunoglobulin (400 milligrams per kilogram every 3 weeks for 1 year) in patients with CLL and hypogammaglobulinemia produced significantly fewer bacterial infections and a significant delay in onset of first infection during the study period.[3] However, there was no effect on survival, routine chronic administration of intravenous immunoglobulin is expensive, and the long-term benefit (more than 1 year) is unproven.[4,5]

Second malignancies and treatment-induced acute leukemias may also occur in a small percentage of patients. Transformation of CLL to diffuse large cell lymphoma (Richter's syndrome) carries a poor prognosis with a median survival of less than 1 year, although 20% of the patients may live more than 5 years after aggressive combination chemotherapy.[6] (A separate summary containing information on adult non-Hodgkin's lymphoma is also available in PDQ.)

Autoimmune hemolytic anemia and/or thrombocytopenia can occur in patients with any stage of CLL. It is frequently advisable to control the autoimmune destruction with corticosteroids, if possible, prior to administering marrow-suppressive chemotherapy because such patients may be difficult to transfuse successfully with either red blood cells or platelets. Alternate therapies include high-dose immune globulin, cyclosporine, splenectomy, and low-dose radiation to the spleen.[7] Tumor lysis syndrome is an uncommon complication (presenting in 1 in 300 patients) of chemotherapy for patients with bulky disease.[8]

About 1% of morphologic CLL cases express T-cell markers (CD4 and CD7) and have clonal rearrangements of their T-cell receptor genes. These patients have a higher frequency of skin lesions, more variable lymphocyte shape, and shorter median survival (13 months) with minimal responses to chemotherapy.[9]

The designations in PDQ that treatments are "standard" or "under clinical evaluation" are not to be used as a basis for reimbursement determinations.

References:

  1. Faguet GB: Chronic lymphocytic leukemia: an updated review. Journal of Clinical Oncology 12(9): 1974-1990, 1994.

  2. Zwiebel JA, Cheson BD: Chronic lymphocytic leukemia: staging and prognostic factors. Seminars in Oncology 25(1): 42-59, 1998.

  3. Cooperative Group for the Study of Immunoglobulin in Chronic Lymphocytic Leukemia: Intravenous immunoglobulin for the prevention of infection in chronic lymphocytic leukemia: a randomized, controlled clinical trial. New England Journal of Medicine 319(14): 902-907, 1988.

  4. Griffiths H, Brennan V, Lea J, et al.: Crossover study of immunoglobulin replacement therapy in patients with low-grade B-cell tumors. Blood 73(2): 366-368, 1989.

  5. Weeks JC, Tierney MR, Weinstein MC: Cost effectiveness of prophylactic intravenous immune globulin in chronic lymphocytic leukemia. New England Journal of Medicine 325(2): 81-86, 1991.

  6. Robertson LE, Pugh W, O'Brien S, et al.: Richter's syndrome: a report on 39 patients. Journal of Clinical Oncology 11(10): 1985-1989, 1993.

  7. Rozman C, Montserrat E: Chronic lymphocytic leukemia. New England Journal of Medicine 333(16): 1052-1057, 1995.

  8. Cheson BD, Frame JN, Vena D, et al.: Tumor lysis syndrome: an uncommon complication of fludarabine therapy of chronic lymphocytic leukemia. Journal of Clinical Oncology 16(7): 2313-2320, 1998.

  9. Hoyer JD, Ross CW, Li CY, et al.: True T-cell chronic lymphocytic leukemia: a morphologic and immunophenotypic study of 25 cases. Blood 86(3): 1163-1169, 1995.


STAGE 0 CHRONIC LYMPHOCYTIC LEUKEMIA

Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. Refer to the PDQ levels of evidence summary for more information.

Because of the indolent nature of stage 0 chronic lymphocytic leukemia (CLL), treatment is not indicated.[1] The French Cooperative Group on Chronic Lymphocytic Leukemia randomized 1535 patients with previously untreated stage A disease to receive either chlorambucil or no treatment and found no survival advantage for immediate treatment with chlorambucil.[2][Level of evidence: 1iiA]

References:

  1. International Workshop on CLL: Prognostic features of early chronic lymphocytic leukaemia. Lancet 2(8669): 968-969, 1989.

  2. Dighiero G, Maloum K, et al. for the French Cooperative Group on Chronic Lymphocytic Leukemia: Chlorambucil in indolent chronic lymphocytic leukemia. New England Journal of Medicine 338(21): 1506-1514, 1998.


STAGE I CHRONIC LYMPHOCYTIC LEUKEMIA

Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. Refer to the PDQ levels of evidence summary for more information.

Observation in asymptomatic or minimally affected patients. The French Cooperative Group on Chronic Lymphocytic Leukemia randomized 1535 patients with previously untreated stage A disease to receive either chlorambucil or no treatment and found no survival advantage for chlorambucil.[1][Level of evidence: 1iiA]

Treatment options:

1. Observation alone.[1]

2. Chemotherapy with oral alkylating agents (for example, chlorambucil or cyclophosphamide in standard doses) with or without corticosteroids (for example, prednisone or prednisolone).

(Note: Prophylactic use of hydration and allopurinol
should be considered when treating patients with large lymph node
masses.)[2,3]

A randomized study compared therapy with chlorambucil to
cyclophosphamide/vincristine/prednisone (COP) in patients with stage
B CLL. Overall survival was identical in both groups.[4]

3. Fludarabine [5] or 2-chlorodeoxyadenosine.[6]

4. Involved-field radiation therapy.

Relatively low doses of radiation will effect an excellent response
for months or years. Sometimes radiation of one nodal area or the
spleen will result in abscopal effect (shrinkage of lymph node tumors
in untreated sites).

References:

  1. Dighiero G, Maloum K, et al. for the French Cooperative Group on Chronic Lymphocytic Leukemia: Chlorambucil in indolent chronic lymphocytic leukemia. New England Journal of Medicine 338(21): 1506-1514, 1998.

  2. Keller JW, Knospe WH, Raney M, et al: Treatment of chronic lymphocytic leukemia using chlorambucil and prednisone with or without cycle-active consolidation chemotherapy: A Southeastern Cancer Study Group trial. Cancer 58(6): 1185-1192, 1986.

  3. Sawitsky A, Rai KR, Glidewell O, et al.: Comparison of daily versus intermittent chlorambucil and prednisone therapy in the treatment of patients with chronic lymphocytic leukemia. Blood 50(6): 1049-1059, 1977.

  4. French Cooperative Group on Chronic Lymphocytic Leukemia: A randomized clinical trial of chlorambucil versus COP in stage B chronic lymphocytic leukemia. Blood 75(7): 1422-1425, 1990.

  5. O'Brien S, Kantarjian H, Beran M, et al.: Results of fludarabine and prednisone therapy in 264 patients with chronic lymphocytic leukemia with multivariate analysis-derived prognostic model for response to treatment. Blood 82(6): 1695-1700, 1993.

  6. Saven A, Lemon RH, Kosty M, et al.: 2-Chlorodeoxyadenosine activity in patients with untreated chronic lymphocytic leukemia. Journal of Clinical Oncology 13(3): 570-574, 1995.


STAGE II CHRONIC LYMPHOCYTIC LEUKEMIA

Treatment options:

1. Observation in asymptomatic or minimally affected patients.

2. Oral alkylating agents with or without corticosteroids. A randomized study compared therapy with chlorambucil to cyclophosphamide/vincristine/prednisone (COP) in patients with stage B chronic lymphocytic leukemia. Overall survival was identical in both groups.[1] Fludarabine, 2-chlorodeoxyadenosine, or pentostatin also resulted in a significant number of durable responses.[2-5]

3. The use of biologic response modifiers is under clinical evaluation. Patients with stage II, III, and IV disease are appropriate candidates for clinical trials.[6]

4. Splenic irradiation alone for palliation of hypersplenism.[7]

References:

  1. French Cooperative Group on Chronic Lymphocytic Leukemia: A randomized clinical trial of chlorambucil versus COP in stage B chronic lymphocytic leukemia. Blood 75(7): 1422-1425, 1990.

  2. O'Brien S, Kantarjian H, Beran M, et al.: Results of fludarabine and prednisone therapy in 264 patients with chronic lymphocytic leukemia with multivariate analysis-derived prognostic model for response to treatment. Blood 82(6): 1695-1700, 1993.

  3. Tallman MS, Hakimian D, Zanzig C, et al.: Cladribine in the treatment of relapsed or refractory chronic lymphocytic leukemia. Journal of Clinical Oncology 13(4): 983-988, 1995.

  4. Saven A, Lemon RH, Kosty M, et al.: 2-Chlorodeoxyadenosine activity in patients with untreated chronic lymphocytic leukemia. Journal of Clinical Oncology 13(3): 570-574, 1995.

  5. Dillman RO, Mick R, McIntyre OR: Pentostatin in chronic lymphocytic leukemia: a phase II trial of Cancer and Leukemia Group B. Journal of Clinical Oncology 7(4): 433-438, 1989.

  6. Byrd JC, Rai KR, Sausville EA, et al.: Old and new therapies in chronic lymphocytic leukemia: now is the time for a reassessment of therapeutic goals. Seminars in Oncology 25(1): 65-74, 1998.

  7. Guiney MJ, Liew KH, Quong GG, et al.: A study of splenic irradiation in chronic lymphocytic leukemia. International Journal of Radiation Oncology, Biology, Physics 16(1): 225-229, 1989.


STAGE III CHRONIC LYMPHOCYTIC LEUKEMIA

Treatment options:

1. Alkylating agents plus corticosteroids.

2. Fludarabine [1] or 2-chlorodeoxyadenosine.[2]

3. Combination chemotherapy.[3]

4. Bone marrow transplantation, autologous or allogeneic, is under clinical evaluation.[4-6]

5. Splenectomy or splenic irradiation may be helpful in patients with hypersplenism or for patients with the complications of immune mediated thrombocytopenia or hemolytic anemia who fail to respond to alkylating agents and prednisone.[7,8]

6. The use of biologic response modifiers is under clinical evaluation. Patients with stage II, III, and IV disease are appropriate candidates for clinical trials.[9]

References:

  1. O'Brien S, Kantarjian H, Beran M, et al.: Results of fludarabine and prednisone therapy in 264 patients with chronic lymphocytic leukemia with multivariate analysis-derived prognostic model for response to treatment. Blood 82(6): 1695-1700, 1993.

  2. Saven A, Lemon RH, Kosty M, et al.: 2-Chlorodeoxyadenosine activity in patients with untreated chronic lymphocytic leukemia. Journal of Clinical Oncology 13(3): 570-574, 1995.

  3. French Cooperative Group on Chronic Lymphocytic Leukemia: Is the CHOP regimen a good treatment for advanced CLL? Results from two randomized clinical trials. Leukemia and Lymphoma 13(5/6): 449-456, 1994.

  4. Khouri IF, Keating MJ, Vriesendorp HM, et al.: Autologous and allogeneic bone marrow transplantation for chronic lymphocytic leukemia: preliminary results. Journal of Clinical Oncology 12(4): 748-758, 1994.

  5. Michallet M, Archimbaud E, Bandini G, et al.: HLA-identical sibling bone marrow transplantation in younger patients with chronic lymphocytic leukemia. Annals of Internal Medicine 124(3): 311-315, 1996.

  6. Rabinowe SN, Soiffer RJ, Gribben JG, et al.: Autologous and allogeneic bone marrow transplantation for poor prognosis patients with B-cell chronic lymphocytic leukemia. Blood 82(4): 1366-1376, 1993.

  7. Neal TF, Tefferi A, Witzig TE, et al.: Splenectomy in advanced chronic lymphocytic leukemia: a single institution experience with 50 patients. American Journal of Medicine 93(4): 435-440, 1992.

  8. Seymour JF, Cusack JD, Lerner SA, et al.: Case/control study of the role of splenectomy in chronic lymphocytic leukemia. Journal of Clinical Oncology 15(1): 52-60, 1997.

  9. Byrd JC, Rai KR, Sausville EA, et al.: Old and new therapies in chronic lymphocytic leukemia: now is the time for a reassessment of therapeutic goals. Seminars in Oncology 25(1): 65-74, 1998.


STAGE IV CHRONIC LYMPHOCYTIC LEUKEMIA

Treatment options:

1. Alkylating agents plus corticosteroids.

2. Fludarabine [1] or 2-chlorodeoxyadenosine.[2]

3. Combination chemotherapy and new single agents.[3]

4. Bone marrow transplantation, autologous or allogeneic, is under clinical evaluation.[4,5]

5. Splenectomy or splenic irradiation may be helpful in patients with hypersplenism or for patients with the complications of immune mediated thrombocytopenia or hemolytic anemia who fail to respond to alkylating agents and prednisone.[6,7]

6. The use of biologic response modifiers is under clinical evaluation. Patients with stage II, III, and IV disease are appropriate candidates to consider for clinical trials.[8]

References:

  1. O'Brien S, Kantarjian H, Beran M, et al.: Results of fludarabine and prednisone therapy in 264 patients with chronic lymphocytic leukemia with multivariate analysis-derived prognostic model for response to treatment. Blood 82(6): 1695-1700, 1993.

  2. Saven A, Lemon RH, Kosty M, et al.: 2-Chlorodeoxyadenosine activity in patients with untreated chronic lymphocytic leukemia. Journal of Clinical Oncology 13(3): 570-574, 1995.

  3. French Cooperative Group on Chronic Lymphocytic Leukemia: Is the CHOP regimen a good treatment for advanced CLL? Results from two randomized clinical trials. Leukemia and Lymphoma 13(5/6): 449-456, 1994.

  4. Khouri IF, Keating MJ, Vriesendorp HM, et al.: Autologous and allogeneic bone marrow transplantation for chronic lymphocytic leukemia: preliminary results. Journal of Clinical Oncology 12(4): 748-758, 1994.

  5. Michallet M, Archimbaud E, Bandini G, et al.: HLA-identical sibling bone marrow transplantation in younger patients with chronic lymphocytic leukemia. Annals of Internal Medicine 124(3): 311-315, 1996.

  6. Neal TF, Tefferi A, Witzig TE, et al.: Splenectomy in advanced chronic lymphocytic leukemia: a single institution experience with 50 patients. American Journal of Medicine 93(4): 435-440, 1992.

  7. Seymour JF, Cusack JD, Lerner SA, et al.: Case/control study of the role of splenectomy in chronic lymphocytic leukemia. Journal of Clinical Oncology 15(1): 52-60, 1997.

  8. Byrd JC, Rai KR, Sausville EA, et al.: Old and new therapies in chronic lymphocytic leukemia: now is the time for a reassessment of therapeutic goals. Seminars in Oncology 25(1): 65-74, 1998.


REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA

Clinical trials are appropriate and should be considered when possible.[1] Refer to PDQ for information regarding ongoing clinical trials for patients with refractory chronic lymphocytic leukemia. Bone marrow transplantation, autologous or allogeneic, is under clinical evaluation.[2,3]

References:

  1. Byrd JC, Rai KR, Sausville EA, et al.: Old and new therapies in chronic lymphocytic leukemia: now is the time for a reassessment of therapeutic goals. Seminars in Oncology 25(1): 65-74, 1998.

  2. Khouri IF, Keating MJ, Vriesendorp HM, et al.: Autologous and allogeneic bone marrow transplantation for chronic lymphocytic leukemia: preliminary results. Journal of Clinical Oncology 12(4): 748-758, 1994.

  3. Michallet M, Archimbaud E, Bandini G, et al.: HLA-identical sibling bone marrow transplantation in younger patients with chronic lymphocytic leukemia. Annals of Internal Medicine 124(3): 311-315, 1996.

Date Last Modified: 05/1999



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