Outocomes of Second Unrelated Cord Blood Transplant for Relapse After First Allogeneic Transplant In Adult Patients with Progressive Acute Myeloid Leukimia/Myelodysplastic Syndrome.

Disease relapse following allogeneic hematopoietic stem cell transplant (allo-HSCT) remains a major cause of treatment failure, often with a poor outcome. Some recent reports have demonstrated successful treatment receiving 2nd allo-HSCT with bone marrow (BM) and peripheral blood (PB) following relapse. However, there are few reports about unrelated cord blood transplant (UCBT). Therefore, we retrospectively analyzed the results of 2nd allo-HSCT using UCB for 34 adult patients with acute myeloid leukemia (AML) / myelodysplastic syndrome (MDS), who relapsed after 1st HSCT.

We reviewed medical records of 130 adult patients with AML/MDS who received 1st HSCT between March 2006 and May 2009 at Toranomon Hospital, Tokyo, Japan. Fifty-three of these patients relapsed after 1st allo-HSCT including 12 recipients of related peripheral blood (RPB), 13 unrelated bone marrow (UBM) and 28 UCB. In these relapsed patients, 34 proceeded to 2nd transplant with UCB. The remaining 19 patients did not receive 2nd transplants because of severe organ dysfunction or uncontrolled active infection and continued complete remission by donor lymphocyte infusion. The median age at 2nd UCBT was 54 years (18-69) and interval between 1st allo-HSCT and 2nd UCBT was 9 months (1-54). Diagnoses include de novo AML (n=21) and MDS overt AML (n=13). Disease status at 1st allo-HSCT were as follows; 4 patients in CR, 25 patients in chemo-refractory and 5 patients in progressive desease without chemotherapy. All patients at 2nd UCBT were in progressive disease. All patients received a single cord blood unit with median TNC/CD34 cell dose of 2.8×10⁷/kg (range, 1.4–4.8) and 0.7×10⁵/kg (range, 0.2–2.2), respectively. HLA disparities were 3/6 match (n=4), 4/6 (n=25), 5/6 (n=4) and 6/6 (n=1). Conditioning regimen consisted of fludarabine and alkylating agent. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus (Tac) alone in 15, Tac plus mycophenolate mofetil in 11, and cyclosporine alone in 8.

Ten patients died by day 28 because of progressive disease (n=5) and transplant related mortality (n=5) and 21 of 24 patients, who survived more than 28 days, were engrafted with complete donor type chimerism (median 19 days). Acute GVHD developed in 14, and chronic GVHD in 4 of these 21 engrafted patients. Estimated 3-year over all survival (OS), transplant related mortality rate and relapse mortality rate were 16%, 32%, and 52%. In univariate analysis, a variable associated with worsened survival were early relapse within 100 days after 1st allo-HSCT (0 vs 21% in late relapses; P=0.01), while other factors were not significant. Eighteen of 19 patients who did not undergo 2nd UCBT died of progressive disease or multiple organ failure.

3 year-OS of 16% with 2nd UCBT following relapsed AML/ MDS was comparable with that of 2nd BMT or PBCST. Considering that all patients in this study were in non-remission and in relatively higher age (median age 54 years), 2nd UCBT following relapse of AML/MDS could be a viable therapeutic option.

No relevant conflicts of interest to declare.