Autologous Stem Cell Transplantation in Patients of High and Intermediate Risk Acute Myeloid Leukemia:-Perspective of a Developing Country.

Most patients with acute myeloid leukemia (AML) who achieve a complete remission after induction chemotherapy will relapse if they do not receive effective consolidation therapy particularly patients of high and intermediate risk. Standard chemotherapy only achieves less than 30% overall survival at 2 years. The most effective consolidation for high risk and intermediate risk patients is allogeneic stem cell transplantation (allo-SCT) which may be related or unrelated. However in the developing world availability of a human leucocyte antigen (HLA) matched donor for those lacking a sibling match is rarely available due to minority of voluntary donors from Indian subcontinent in various registries. Hence autologous stem cell transplant (auto-SCT) is one option that has been studied extensively. The question as to whether auto-SCT after consolidation chemotherapy improves the probability of survival of patients with AML has not been settled. In view of the above considerations, we carried out a retrospective study aimed at analyzing the impact of disease, patient, and transplantation-related factors on relapse, non–leukemia-related death, and LFS of patients with AML.

We present here retrospective data of 16 patients of AML who undergone auto SCT in our centre from Jan 2005 to Jan 2009. The median age of patients was 24 yrs with a range from 10 to 40 years. Male: Female ratio was 11:5. The diagnosis was established on both bone marrow morphology and immunophenotyping study. Morphologically there was 1 case each of AML-M1, AML-M4, AML-M5, AML-M6 and rest 13 cases were of AML-M2. Bone marrow karyotyping was done in 11 cases. Out of 11 cases where karyotyping was done, 2 were metaphase failures; 1 was deletion 7; 1 was trisomy 8 and rest had normal cytogenetics. All cases were classified as high risk or intermediate risk either by cytogenetics or by other standard criteria. All patients received standard induction chemotherapy (Idarubicin x 3days, Cytosine CI x 7days) followed by 2 or 3 high dose Cytosine. Fourteen patients were in first remission (CR-1) while 2 patients were in CR-2 (one case of AML-M5 with deletion 7 and one AML-M4 with normal cytogenetics). None of the patients had a related HLA matched donor and all patients underwent auto-SCT, the graft being peripheral blood stem cell.

The conditioning regimen for initial 6 cases were Busulfan(16mg/kg over 4 days) and Cyclophosphamide(120mg/kg over 2 days)(BuCy) and the remaining 10 cases were adminstered Idarubicin (60mg/mt2 over 3days) and Busulfan (16mg/kg over 4 days) (IBu). All cases engrafted except one patient who died due to sepsis on 6^th day post SCT prior to engraftment. The median engraftment for neutrophil was day10 (9-14) and platelet was on day 16 (13 - 20).

Nine out of 16 patients are alive and free from leukemia on median follow up of 38 (18 to 56 months). Five patients died due to leukemia relapse; 1 patient had transplant related mortality (Sepsis) and 1 patient died due to unrelated cause (Severe heat exertion with multiorgan failure). The overall (OS) and leukemia free survival (LFS) on a median follow up of 38 months was 56.25% which is better than the chemotherapy group. The treatment related mortality (TRM) was 6.25%. Both patients transplanted in CR-2 relapsed and died. Three out of 6 patients from BuCy and 6 out 10 from IBu conditioning are alive. Out of 9 patients surviving, 5 had normal karyotype while in 4 same was not known. The patients with deletion 7 and trisomy 8 died due to leukemia relapse.

Auto-SCT is a viable option for AML patients who are in need of a allo-SCT but do not have a donor. However larger studies would be required to establish the exact role of auto-SCT in AML.

No relevant conflicts of interest to declare.