Phase II Study of Chemotherapy (Cx) and Stem Cell Transplantation (SCT) for Adult Acute Lymphoblastic Leukemia (ALL) and Lymphoblastic Lymphoma (LBL): Long-Term Follow-up Results of Japan Clinical Oncology Group (JCOG) Study 9402.

To evaluate the efficacy and safety profile of an intensive induction and post-remission Cx for untreated patients (pts) with adult ALL and LBL, focusing on the long-term follow-up results. Feasibility and efficacy of autologous or allogeneic SCT were also assessed.

We enrolled pts with untreated adult ALL or LBL aged 15 to 69 years. The Cx regimen consisted of induction Cx (vincristine [VCR], cyclophosphamide [CPA], prednisone [PSL], doxorubicin [DXR], L-asparaginase plus intrathecal methotrexate [IT-MTX]) followed by two consolidation Cx regimens (Consolidation A, consisting of daunorubicin, cytosine arabinoside [Ara-C], vindesine [VDS], PSL plus IT-MTX; Consolidation B, consisting of CPA, Ara-C, 6-mercaptopurine [6-MP], VCR plus IT-MTX) with the prophylactic use of granulocyte colony-stimulating factor. Thereafter, interim maintenance Cx including 6-MP and MTX concurrent with CNS prophylaxis (IT-MTX), intensification Cx (VCR, DXR, PSL, CPA, Ara-C and 6-MP) and maintenance Cx (VDS, CPM, PSL, DXR, MTX and 6-MP) were sequentially performed for two years. For pts with 50 years or younger who achieved complete remission (CR) after induction Cx, allogeneic SCT for ALL from HLA-matched related donor and autologous SCT for LBL were to be considered. Primary endpoint was 5-year progression-free survival (PFS). Secondary endpoints included CR rate (%CR), overall survival (OS) and adverse events.

Among 115 pts who were enrolled between 1994 and 1999, 108 eligible pts (median age, 33.5 years [15-69]) including 96 ALL and 12 LBL pts who received induction Cx were assessed. Seven pts were judged ineligible, including four histologically ineligible pts revealed by institutional or central review. Other major characteristics of the 108 eligible pts were as follows: 54 males (50%); T-cell phenotype, 23 pts (21%); Ph, 24 pts (22%); t(4;11), 2 pts (2%); B-symptom+, 38 pts (35%); PS 2/3, 24 pts (22%). Eighty-seven pts achieved CR (%CR 81%; 95% CI, 72-88%), while five patients (5%) died during induction Cx mainly due to infections. The median OS and the median PFS of the 108 eligible pts were 1.8 years (95% CI, 1.5-2.6 years) and 1.2 years (95% CI, 0.8-1.6 years), respectively. Their 5-year OS and 5-year PFS were 29% and 28%, respectively, with the median follow-up of the censored cases of 9.3 years (range, 2.0-12.3 years). The 5-year OS from the date of SCT of 31 pts who underwent allogeneic (n=19) or autologous (n=12) SCT during 1st CR was 51% (95% CI, 32-67%). Major non-hematologic toxicities of grade 3 or greater included infections (n=24, 21%), pulmonary complications (n=7, 6%) and diarrhea (n=7, 6%). As compared with the investigators' previous phase II trials for ALL and LBL, JCOG9402 improved PFS and OS as compared with JCOG8702 (MST, 1.2 years; 7-year OS, 15%; 7-year PFS, 13%) (Jpn J Clin Oncol 1999;29:340), but did not show improvement as compared with JCOG9004 (MST, 2.2 years; 5-year OS, 32%; 5-year PFS, 26%) (Cancer Sci 2007;98:1350).

Although the intensified induction and post-remission Cx was feasible and 28% of pts achieved long-term PFS, JCOG9402 failed to show improvement in long-term follow-up results as compared with the investigators' latest historical control. To further improve the therapeutic outcomes of adult pts with ALL and LBL, novel strategies are warranted.

No relevant conflicts of interest to declare.