Early donor chimerism in patients with myeloid malignancies undergoing stem cell transplantation using FluBu4 with and without busulfan pharmacokinetics compared to busulfan and cyclophosphamide.
Farhan S, Neme K, Mikulandric N, Ruemenapp K, Trapp MA, Bazydlo M, Peres E, and Janakiraman N. Early donor chimerism in patients with myeloid malignancies undergoing stem cell transplantation using FluBu4 with and without busulfan pharmacokinetics compared to busulfan and cyclophosphamide. Biol Blood Marrow Transplant 2017; 23(3):S271.
Biology of Blood and Marrow Transplantation
The impact of early donor cell chimerism on outcomes of reduced toxicity conditioning regimens and allogeneic stem cell transplantation (SCT) in myeloid disorders is ill defined. To explore the impact of busulfan pharmacokinetics (Bu PK) on early donor chimerism, we undertook a retrospective analysis of patients with myeloid disorders in the last 10 years who received four days of fludarabine and busulfan (FluBu4) with or without measuring Bu PK and those who got busul-fan with cyclophosphamide (BuCy). Methods: Chimerism assay was performed using a quantitative fluorescence-based short tandem repeat-polymerase chain reaction (STR-PCR) with capillary electrophoresis for PCR product resolution. Results: In this study, 75 patients were identified and included. Fifty two patients got FluBu4, of whom 21 had Bu PK measured. BuCy was given in 32 patients. There were 48 males and 27 females with a median age of 59 years. Disease risk index (DRI) was high or very high in 52%, 48% and 60% of pa-tients in the FluBu4 with Pk, no PK and BuCY, respectively. Thirty six patients had matched related donor (MRD), 31 had matched unrelated donor and 8 had mismatched unrelated donor SCT. Total donor cell chimerism analysis showed that the odd ratio (OR) for not having 100% chimerism at day 100 is 4.4 (CI 1.38 to 14.57; P =.01) for FluBu4 without PK compared to BuCY, while OR was 1.4 for FluBu4 with PK compared to BuCy (P =.59). In addition, OR was 3.1 (CI.99 to 10.10, P =.05) for FluB4 without PK to the group with PK. For decreasing total chimerism on day 100, the OR for FluB4 no PK and BuCy was 3 (P =.06) while it was.8 for the group with PK compared to BuCy (P =.86). OR between no PK group and those with PK for decreasing donor chimerism at day 100 was 3.4 (CI 1.00 to 11.63, P =.04). For day 30 chimerism, to have <95% total chimersim, OR FluBu4 no PK compared to BuCy was 1.65 (P =.4) while OR comparing FluB4 with PK to BuCy was.2 (CI.02 to 2.32, P =.2). OR comparing between group without Pkand with PK for <95% at day 30 was 6.9 (P =.07). Relapse rate was 24%, 45% and 57% for FluBu4 with PK, FluBu4 no PK and BuCy respectively, P =.085). Survival distributions of the three treatment groups were not statistically significant (P =.11) Figure 1. Conclusion: In this small cohort, we found that patients with myeloid disorders who got FluBu4 with Bu PK had a trend for higher donor chimerism similar to BuCy at day100. While FluB4 with no PK has tendency to loose donor chimerism by day 100 and has more of <95% donor chimerism on day 30. Previous studies showed that low or decreasing donor chi-merism early after SCT is an independent risk factor for relapse and impaired survival. This is especially important in myeloid disorders. These results should be interpreted with caution given the retrospective design of the study, the small number of patients and the need for longer follow up.