Improved outcome in adult B-cell acute lymphoblastic leukemia.

A total of 68 adult patients with B-cell acute lymphoblastic leukemia (B-ALL) were treated in three consecutive adult multicenter ALL studies. The diagnosis of B-ALL was confirmed by L3 morphology and/or by surface immunoglobulin (Slg) expression with > 25% blast cell infiltration in the bone marrow (BM). They were characterized by male predominance (78%) and a median age of 34 years (15 to 65 y) with only 9% adolescents (15 to 20 y), but 28% elderly patients (50 to 65 y). The patients received either a conventional (N = 9) ALL treatment regimen (ALL study 01/81) or protocols adapted from childhood B-ALL with six short, intensive 5-day cycles, alternately A and B. In study B-NHL83 (N = 24) cycle A consisted of fractionated doses of cyclophosphamide 200 mg/m2 for 5 days, intermediate-dose methotrexate (IdM) 500 mg/m2 (24 hours), in addition to cytarabine (AraC), teniposide (VM26) and prednisone. Cycle B was similar except that AraC and VM26 were replaced by doxorubicin. Major changes in study B-NHL86 (N = 35) were replacement of cyclophosphamide by ifosphamide 800 mg/m2 for 5 days, an increase of IdM to high-dose, 1,500 mg/m2 (HdM) and the addition of vincristine. A cytoreductive pretreatment with cyclophosphamide 200 mg/m2, and prednisone 60 mg/m2, each for 5 days was recommended in study B-NHL83 for patients with high white blood cell (WBC) count (> 2,500/m2) or large tumor burden and was obligatory for all patients in study B-NHL86. Central nervous system (CNS) prophylaxis/treatment consisted of intrathecal methotrexate (MTX) therapy, later extended to the triple combination of MTX, AraC, and dexamethasone, and a CNS irradiation (24 Gy) after the second cycle. Compared with the ALL 01/81 study where all the patients died, results obtained with the pediatric protocols B-NHL83 and B-NHL86 were greatly improved. The complete remission (CR) rates increased from 44% to 63% and 74%, the probability of leukemia free survival (LFS) from 0% to 50% and 71% (P = .04), and the overall survival rates from 0% to 49% and 51% (P = .001). Toxicity, mostly hematotoxicity and mucositis, was severe but manageable. In both studies B-NHL83 and B-NHL86, almost all relapses occurred within 1 year. The time to relapse was different for BM, 92 days, and for isolated CNS and combined BM and CNS relapses, 190 days (P = .08). The overall CNS relapses changed from 50% to 57% and 17%, most probably attributable to the high-dose MTX and the triple intrathecal therapy. LFS in studies B-NHL83 and B-NHL86 was significantly influenced by the initial WBC count < or > 50,000/microL, LFS 71% versus 29% (P = .003) and hemoglobin value > or < 8 g/dL, LFS 67% versus 27% (P = .02). Initial CNS involvement had no adverse impact on the outcome. Elderly B-ALL patients (> 50 years) also benefited from this treatment with a CR rate of 56% and a LFS of 56%. It is concluded that this short intensive therapy with six cycles is effective in adult B-ALL. HdM and fractionated higher doses of cyclophosphamide or ifosphamide seem the two major components of treatment.

[1]  E. Copelan,et al.  The biology and treatment of acute lymphoblastic leukemia in adults. , 1995, Blood.

[2]  P. Cony-Makhoul,et al.  Small noncleaved cell lymphoma and leukemia in adults. A retrospective study of 65 adults treated with the LMB pediatric protocols. , 1995, Blood.

[3]  H. Kantarjian Adult acute lymphocytic leukemia: critical review of current knowledge. , 1994, The American journal of medicine.

[4]  G. Leverger,et al.  7 Therapy of Burkitt and other B-cell acute lymphoblastic leukaemia and lymphoma: Experience with the LMB protocols of the SFOP (French Paediatric Oncology Society) in children and adults , 1994 .

[5]  H. Löffler,et al.  3 Morphology and cytochemistry of acute lymphoblastic leukaemia , 1994 .

[6]  F Lampert,et al.  Favorable outcome of B-cell acute lymphoblastic leukemia in childhood: a report of three consecutive studies of the BFM group. , 1992, Blood.

[7]  A. Look,et al.  Accumulation of high levels of methotrexate polyglutamates in lymphoblasts from children with hyperdiploid (greater than 50 chromosomes) B-lineage acute lymphoblastic leukemia: a Pediatric Oncology Group study. , 1992, Blood.

[8]  F. Menestrina,et al.  Mediastinal large-B-cell lymphoma with sclerosis: a clinical study of 21 patients. , 1990, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[9]  P. Fenaux,et al.  Burkitt cell acute leukaemia (L3 ALL) in adults: a report of 18 cases , 1989, British journal of haematology.

[10]  A. Hagemeijer,et al.  TdT positive B‐cell acute lymphoblastic leukaemia (B‐ALL) without Burkitt characteristics , 1988, British journal of haematology.

[11]  C. Pui,et al.  Results of treatment of advanced-stage Burkitt's lymphoma and B cell (SIg+) acute lymphoblastic leukemia with high-dose fractionated cyclophosphamide and coordinated high-dose methotrexate and cytarabine. , 1986, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[12]  T. Lister,et al.  Treatment of acute lymphoblastic leukaemia in adults , 1986, British journal of haematology.

[13]  A. Bernard,et al.  Improved survival rate in children with stage III and IV B cell non-Hodgkin's lymphoma and leukemia using multi-agent chemotherapy: results of a study of 114 children from the French Pediatric Oncology Society. , 1986, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[14]  A. Levine,et al.  B cell acute lymphocytic leukemia in adults. Clinical, morphologic, and immunologic findings. , 1986, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[15]  M. Andreeff,et al.  Acute lymphoblastic leukemia in adults. , 1985, Seminars in oncology.

[16]  G. Henze,et al.  Kindliche B-Zell-Lymphome und -Leukämien , 1984 .

[17]  E. Thiel,et al.  Intensified therapy in acute lymphoblastic and acute undifferentiated leukemia in adults. , 1984, Blood.

[18]  M. Baccarani,et al.  Adolescent and adult acute lymphoblastic leukemia: prognostic features and outcome of therapy. A study of 293 patients. , 1982, Blood.

[19]  G. Zei,et al.  Adult acute lymphoblastic leukemia. Response to therapy according to presenting features in 62 patients. , 1982, European journal of cancer & clinical oncology.

[20]  Murphy Sb Classification, staging and end results of treatment of childhood non-Hodgkin's lymphomas: dissimilarities from lymphomas in adults. , 1980 .

[21]  J. Finlay,et al.  Acute lymphoblastic leukemia with Burkitt cell morphology and cytoplasmic immunoglobulin. , 1980, Blood.

[22]  A. Lichtenstein,et al.  Primary mediastinal lymphoma in adults. , 1980, The American journal of medicine.

[23]  J. Ziegler Treatment results of 54 American patients with Burkitt's lymphoma are similar to the African experience. , 1977, The New England journal of medicine.

[24]  Jung Sun Kim,et al.  Methotrexate and citrovorum factor rescue in the management of childhood lymphosarcoma and reticulum cell sarcoma (non‐Hodgkin's lymphomas). Prolonged Unmaintained Remissions , 1976, Cancer.

[25]  H. Gralnick,et al.  Proposals for the Classification of the Acute Leukaemias French‐American‐British (FAB) Co‐operative Group , 1976, British journal of haematology.

[26]  J. Bertino,et al.  S-phase cells of rapidly growing and resting populations. Differences in response to methotrexate. , 1969, Molecular pharmacology.

[27]  N. Mantel Evaluation of survival data and two new rank order statistics arising in its consideration. , 1966, Cancer chemotherapy reports.

[28]  E. Kaplan,et al.  Nonparametric Estimation from Incomplete Observations , 1958 .

[29]  H. Löffler,et al.  Morphology and cytochemistry of acute lymphoblastic leukaemia. , 1994, Bailliere's clinical haematology.

[30]  E. Thiel,et al.  Immunophenotypic features of childhood and adult acute lymphoblastic leukemia (ALL): experience of the German Multicentre Trials ALL-BFM and GMALL. , 1994, Leukemia & lymphoma.

[31]  G. Leverger,et al.  Therapy of Burkitt and other B-cell acute lymphoblastic leukaemia and lymphoma: experience with the LMB protocols of the SFOP (French Paediatric Oncology Society) in children and adults. , 1994, Bailliere's clinical haematology.

[32]  James T. Lin,et al.  Decreased polyglutamylation of methotrexate in acute lymphoblastic leukemia blasts in adults compared to children with this disease. , 1993, Leukemia.

[33]  D. Hoelzer Aggressive chemotherapy of ALL in elderly patients. , 1993, Hematological oncology.

[34]  P. Colombat,et al.  Treatment of poor prognosis Burkitt's lymphoma in adults with the Société Française d'Oncologie Pédiatrique LMB Protocol--a study of the Federation Nationale des Centres de Lutte Contre le Cancer (FNLCC). , 1992, European journal of cancer.

[35]  J. Bosq,et al.  Burkitt's lymphoma in adults: a retrospective study of 46 cases. , 1992, Nouvelle revue francaise d'hematologie.

[36]  H. Weinstein,et al.  HiC-COM: a 2-month intensive chemotherapy regimen for children with stage III and IV Burkitt's lymphoma and B-cell acute lymphoblastic leukemia. , 1991, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[37]  E. Orlandi,et al.  Burkitt's lymphoma/leukemia: a clinicopathologic study on 24 adult patients. , 1991, Leukemia.

[38]  J. Shuster,et al.  Clinical and biological heterogeneity of childhood B cell acute lymphocytic leukemia: implications for clinical trials. , 1990, Leukemia.

[39]  J. Finlay,et al.  Acute B-lymphocytic leukemia with L1 morphology: a report of two pediatric cases. , 1988, Leukemia.

[40]  A. Ganser,et al.  Prognostic factors in a multicenter study for treatment of acute lymphoblastic leukemia in adults , 1988 .

[41]  N. Schmitz,et al.  Morphological and cytochemical classification of adult acute leukemias in two multicenter studies in the Federal Republic of Germany. , 1987, Haematology and blood transfusion.

[42]  D. Huhn,et al.  Clinical relevance of blast cell phenotype as determined with monoclonal antibodies in acute lymphoblastic leukemia of adults. , 1987, Haematology and blood transfusion.

[43]  R. Gale,et al.  Acute lymphoblastic leukemia in adults: recent progress, future directions. , 1987, Seminars in hematology.

[44]  Walker,et al.  Chromosomal abnormalities identify high-risk and low-risk patients with acute lymphoblastic leukemia. , 1986, Blood.

[45]  A. Spiers,et al.  Acute lymphoblastic leukemia of Burkitt's type (L-3 ALL) lacking surface immunoglobulin and the 8;14 translocation. , 1985, American journal of clinical pathology.