Umbilical Cord Blood Transplant after Reduced Intensity Conditioning Provides Outcomes Comparable HLA-Matched Siblings for Patients with High Risk and Advanced Acute Myeloid Leukemia.

Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) is a standard treatment for patients with high risk or advanced AML. However, older age and of co-morbidities frequently limit its use due to high risk of regimen related toxicities (RRT) after a myeloablative regimen. While the inception of RIC regimens has been very successful at reducing RRT, lack of available HLA matched sibling or unrelated donors has become the principal limiting factor. We hypothesized that UCB would increase the utilization of HSCT in patients with AML who lacked a HLA-matched, medically suitable sibling donor. Therefore, we evaluated the various transplant outcomes in 64 AML patients treated with RIC followed by transplantation with HLA-matched sibling PBSC (n=21) and 4–6/6 HLA matched UCB (n=43). All pts received Fludarabine (Flu, 200 mg/kg) and total body irradiation (TBI 200 cGy) with either cyclophosphamide (Cy 50 mg/kg, n=49) or Busulfan (Bu 8 mg/kg, n=15). All pts received cyclosporine A and mycophenolate mofetil GVHD prophylaxis. UCB grafts were composed of 1 (n=15) or 2 (n=28) units to achieve the minimum cell dose. Patients with good and intermediate risk cytogenetics in first complete remission (CR1) were classified as standard risk; others were classified as high risk. Multivariate models considered: donor type, age, disease status, weight, CMV serostatus, cytogenetic risk, disease risk, acute GVHD, conditioning regimen, and time from diagnosis to HSCT. The proportion of engraftment (88% vs. 100%, p=0.10), the incidence of grade II–IV GVHD at day 100 (51% vs. 62%, p=0.85) and TRM at 1 year (28% vs 38%, p=0.43) did not differ between UCB and PBSC recipients. Similarly, relapse at 2 years (UCB 35% vs SIB 35%, p=0.72) and 2 year survival (UCB 31% vs SIB 32%, p=0.62) were comparable. In multivariate analysis, only disease risk group was associated with increased relative risk (RR) of relapse (RR 2.9, 95%CI, 1.3–6.2, p<0.01) and death (RR 2.6, 95%CI, 1.1–5.5, p=0.02). These results demonstrate that partially HLA matched UCB after RIC markedly extends the availability of HSCT with results comparable to those observed with PBSC from HLA matched sibling donors.VariableUCB (n=43)SIB PBSC (n=21)p valueAge in years - median (range)53 (22–68)54 (19–69)0.77Weight in kg - median (range)75 (53–120)72 (51–112)0.24Recipient/Donor CMV +20 (47%)/−13 (62%)/8 (38%)<0.01HLA-match 6/6*5 (7%)21 (100%)HLA-match 4–5/6*66 (93%)ZeroDisease status CR118 (43%)14 (67%)Cytogenetics good/intermediate32 (84%)10 (48%)0.31Cytogenetics poor risk7 (16%)10 (48%)TNC X10 7/kg median (range)*3.6 (1.6–5.9)93.4 (64.8–212.3)CD34 X105/kg median (range)*4.9 (1.1–18.8)52.2 (14.1–153.7)Median follow-up in years2.7 (0.7–5.5)1.3 (0.7–6.1)* Cell doses of double UCB grafts=combined cell dose.