A five-drug remission induction regimen with intensive consolidation for adults with acute lymphoblastic leukemia: cancer and leukemia group B study 8811

Abstract

The goal of this phase II multicenter clinical trial was to evaluate a new intensive chemotherapy program for adults with untreated acute lymphoblastic leukemia (ALL) and to examine prospectively the impact of clinical and biologic characteristics on the outcome. One hundred ninety-seven eligible and evaluable patients (16 to 80 years of age; median, 32 years of age) received cyclophosphamide, daunorubicin, vincristine, prednisone, and L-asparaginase; 167 patients (85%) achieved a complete remission (CR), 13 (7%) had refractory disease, and 17 (9%) died during induction. A higher CR rate was observed in younger patients (94% for those < 30 years old, 85% for those 30 to 59 years old, and 39% for those > or = 60 years old, P < .001) and in those who had a mediastinal mass (100%) or blasts with a T-cell immunophenotype. Eighty percent of B-lineage and 97% of T-cell ALL patients achieved a CR (P = .01). The coexpression of myeloid antigens did not affect the response rate or duration. Seventy percent of those with cytogenetic or molecular evidence of the Philadelphia (Ph) chromosome and 84% of those without such evidence achieved a CR (P = .11). Patients in remission received multiagent consolidation treatment, central nervous system prophylaxis, late intensification, and maintenance chemotherapy for a total of 24 months. After a median follow-up time of 43 months, the median survival for all 197 patients is 36 months; the median remission duration for the 167 CR patients is 29 months. Favorable pretreatment characteristics relative to remission duration or survival are younger age, the presence of a mediastinal mass or lymphadenopathy, a white blood cell count (WBC) less than 30,000/microL, L1 morphology, T or TMy immunophenotype, and the absence of the Ph chromosome. The estimates of the proportion surviving at 3 years are 69% for patients less than 30 years old, 39% for those 30 to 59 years old, 89% for those who had a mediastinal mass, 59% with WBC less than 30,000/microL, 63% with L1 morphology, 69% for T or TMy antigen expression, and 62% for those who lack the Ph chromosome. Fifteen patients (8%) had no unfavorable prognostic factors and have an estimated probability of survival at 5 years of 100% (95% confidence interval, 77% to 100%). This intensive chemotherapy regimen produces a high remission rate and a high proportion of durable remissions in adults with ALL.

Phase II study of chemotherapy and stem cell transplantation for adult acute lymphoblastic leukemia or lymphoblastic lymphoma: Japan Clinical Oncology Group study 9004

“…The proportion of patients with Philadelphia chromosome anomaly in ALL (23/103, 22%) was not different from other reports, and they showed an unfavorable prognosis similar to other studies. (11)(12)(13)(26)(27)(28) C-reactive protein did not have an impact in the present study, in contrast to the authors' previous trial, JCOG 8702. (15) Patients with LBL showed a tendency toward a more favorable prognosis than those with ALL, although there was no significant difference, as shown in Table 6.…”

“…(15) These results using induction therapy are equivalent to those from other multiinstitutional trials. (3,5,6,(9)(10)(11)(12)(13) The major problem in induction therapy was TRD in the older age group. Considering the high incidence of TRD in older age groups (26% [12/46] in patients at ≥50 years and 50% [9/18] in those at ≥60 years) despite the dose reduction in patients at ≥50 years (Table 1), further modifications of dose and schedule in induction therapy may be necessary for older patients.…”

“…(1,(3)(4)(5)(6)(7) Generally, the prognoses of adult patients are unfavorable compared with pediatric patients. (6)(7)(8)(9)(10)(11)(12)(13) In 1981, the Lymphoma Study Group of the Japan Clinical Oncology Group (JCOG-LSG) initiated a phase III trial for non-Hodgkin lymphoma including LBL, using first-generation chemotherapy, VEPA (vincristine [VCR], cyclophosphamide [CPA], prednisolone [PSL] and doxorubicin [DXR]) or VEPA-M (VEPA plus methotrexate [MTX]); however, the outcome for patients with LBL was poor. (14) With the aim of improving the results against LBL, JCOG-LSG conducted a phase II study, JCOG8702, an alternating non-cross-resistant combination chemotherapy consisting of VEPA, L-asparaginase (L-asp) and intermediate-dose MTX without maintenance therapy with 6mercaptopurine (6-MP) and MTX for ALL and LBL.…”

Aberrant T‐cell antigen expression in B lymphoblastic leukaemia

“…Paediatric patients were treated according to the standard Children's Oncology Group (COG) or Dana Farber Cancer Institute (DFCI) research treatment protocols, except for one patient who was treated as per the St. Jude protocol (Albersten, 2000;Cairo, 2000;Dreyer, 2000;Martin, 2000;Pieters, 2000;Pui et al, 2010;Silverman, 2000a,b;Stork et al, 2010;Vrooman et al, 2009;Winick, 2000). Adult patients were treated as per the hyper-CVAD (Thomas et al, 2004) or the Cancer and Leukaemia Group B (CALGB) protocols (Larson et al, 1995). Other clinical parameters reviewed included sex, age, and white blood cell (WBC) count.…”

Initial and late prognostic factors to predict survival in adult acute lymphoblastic leukaemia

“…The prognosis of childhood acute lymphoblastic leukaemia (ALL) has been constantly improving over the past 25 yr; the current cure rates reached 75-80% (1,2). On the contrary, in adults, the prognosis of ALL remains poor; the survival rates at 5 yr still range between 20% and 40% (3)(4)(5)(6)(7)(8). This poor outcome has driven the development of new therapeutic strategies.…”