Effect of Related and Unrelated Donor Haemopoietic Stem-Cell Transplantation on Outcome In Adults with High Risk Acute Leukemia: An Intention-to-Treat Analysis at a Single Center Institution

Allogeneic haemopoietic stem cell transplantation (HSCT) is the best therapeutic option for high-risk hematological disease (HRHD), particularly acute myeloid and lymphoblastic leukemia (AML/ALL). A widely application of HSCT is limited by lack of availability of a suitable donor for every candidate patients (pts). In order to offer a donor to every candidate pts, several centers had developed in the last decade alternative strategy of HSCT, such as umbilical cord blood (UCB) or family haploidentical HSCT (haplo-HSCT). With the aim to treat high-risk leukemia in the ideal appropriate time by allogeneic HSCT, we adopted a policy relying upon HLA typing at entry of every pts diagnosed with HRHD, followed, in absence of a MRD, by the prompt activation of the MUD search. Patients lacking a MRD or a MUD at the appropriate timing are proposed for haplo-HSCT.

Here we report an intention-to-treat analysis of alternative donor HSCT at our Institution for pts diagnosed with high risk AML or ALL. Data were obtained from local institutional database.

Between Jan-2004 and July-2010 241 pts (median age 48y, r 15–72) with diagnosis of ALL (60 pts; median age 33y, r 15–64; male 39) or AML (181 pts, median age 51y, r 19–72; male 83) were defined as “high risk status” and received an indication to HSCT according to EBMT (European Group for Blood and Marrow Transplantation) and Northern Italy Leukemia Group (NILG, www.nilg.it) recommendations.

In the ALL group 3 pts died before proceed to HSCT, 5 pts are waiting for the identification of a donor. Overall, 52/60 (86%) pts underwent HSCT, the status of disease at transplant was of complete remission (CR) for 27 pts, persistence of disease (PD) for 25.

In the AML group 6 pts died before proceed to HSCT, 15 pts are waiting for the identification of a donor. Overall, 160/181 (88%) pts underwent HSCT, the status of disease at transplant was of CR for 97 pts, PD 63.

Overall 92 pts activated the research of a MUD, 42 proceed to transplant, 7 received a UCB, 26 received a haplo-HSCT due to absence of a suitable donor in the appropriate time frame or failure to met the criteria to engage a MUD donor. The median time from diagnosis to registry activation was 69 days (r 5–876), the median time from activation to transplant 84 days (r 28–348).

In the group of pts in CR at transplant, 37 underwent HSCT from a MRD and 36 from a MUD, 4 pts received a UCB and 47 a haplo-HSCT. Seventy-two pts are alive and in CR at last follow-up, 3/72 after a second transplant from a different donor (haplo-HSCT) and 3/72 after chemotherapy and adoptive immunotherapy to treat hematological relapse. Fifty-two pts died and the causes of death were: relapse (27), infection-related (19), graft-versus-host-disease (GvHD; 5), acute myocardial infarction (1).

In the group of pts in PD at transplant, 16 underwent HSCT from a MRD and 6 from a MUD, 3 pts received UCB and 63 a haplo-HSCT. Fifteen pts are alive, 14 in CR, 1 pts under adoptive immunotherapy; 1/14 pts received a second transplant from a different donor (haplo-HSCT) to treat hematological relapse. Seventy-three pts died and the causes of death were: relapse (43), infection (23), GvHD (7).

Overall, the median survival is 382 days and the median follow-up for pts alive is 548 days. The 1-year overall survival (OS)/transplant related mortality (TRM)/relapse incidence (RI) are 50,76% 26,96% and 40% respectively.

For pts transplanted in CR the 1y OS/TRM/RI are 77,2%, 20,01% and 25% respectively. The outcome analysis per donor source (MRD vs MUD vs haplo-HSCT) is comparable (p=ns).

For pts transplanted in PD the 1y OS/TRM/RI are 19,7%, 41% and 67% respectively. The outcome analysis per donor source (MRD vs MUD vs haplo-HSCT) shows a trend of lower RI and TRM in the haplo-SCT vs MRD.

The policy adopted provided an allogeneic HSCT in > 80% of candidate high-risk acute leukemia patients. No significant differences were registered in outcome for patients transplanted from matched-related, unrelated or family haploidentical donors. Further evaluation and a long-term follow-up will add important evaluation in term of long-term disease control and long-term toxicities.

Bonini: MolMed: Consultancy. Bordignon: Molmed: Employment.