Allogeneic Stem Cell Transplantation Should Be Performed in First Complete Remission in Adults with Acute Lymphoblastic Leukemia; Strong Antileukemic Activity of Chronic Graft-Versus-Host Disease.

Purpose: The role of allogeneic stem cell transplantation (SCT) for adult acute lymphoblastic leukemia (ALL) remains unclear because interpretation of transplantation outcome is complicated by the criteria used to select patients for transplantation and by the relatively small number of patients studied. Moreover, whether SCT from an unrelated donor could be a treatment option of equal value in a case lacking a compatible related donor remains controversial. The aim of the present study was to determine the graft-versus-leukemia (GVL) effect and risk factors affecting outcome of 218 adults with ALL who received allogeneic SCT during the last 10 years (1995 to 2004).

Patients and Methods: The study population was 218 consecutive adults receiving an allogeneic SCT from matched sibling (n=162) or unrelated (n=56; 40 matched, 16 mismatched) donors at the Catholic Hematopoietic Stem Cell Transplantation Center in Korea. Their median age was 30 years (range, 15–61 years). One hundred eighty-three (83.9%) patients had high-risk criteria, and of these, 69 (31.7%) had t(9;22)/BCR-ABL and 7 (3.2%) had t(4;11)/MLL-AF4. One hundred sixty-five patients (75.7%) were transplanted in first complete remission (CR1); 23 (10.5%) in CR2; and 30 (13.8%) were resistant to chemotherapy before transplantation. Most patients (n=206, 94.5%) received a preparative treatment of total body irradiation (TBI)-containing regimen (TBI/cyclophosphamide for CR1, TBI/cytarabine/melphalan for >CR1). Graft-versus-host disease (GVHD) prophylaxis was attempted by administering calcineurin inhibitor (cyclosporine for sibling, tacrolimus for unrelated) plus methotrexate.

Results: With a median follow-up of 52 months (range, 15+ to 130+ months) after SCT, the 5-year probability of disease-free survival (DFS) was 51.3%±3.5% for all patients; 62.4%±4.3% for patients in CR1; and 11.3%±4.4% for patients in >CR1 at transplantation. There was no difference in DFS for sibling and unrelated transplant patients in CR1 (65.2%±4.3% v 62.3%±8.0%). Multivariate Cox regression analysis showed that the most powerful predictive factor affecting relapse and DFS was disease status at transplantation (CR1 v >CR1, p<0.001). The presence of chronic GVHD was also found to be significantly associated with favorable outcome (p<0.001).

Conclusion: Our data in combination with recent studies suggest that matched related or unrelated allogeneic SCT should be performed in CR1 in adults with ALL. Further studies to develop treatment strategies to reduce leukemic cell burden and to enhance GVL effect are needed. The indications for allogeneic SCT also should be continuously evaluated.