A patient with AML developed severe respiratory distress and died after receiving gemtuzumab and 6 units of platelets on the same day. The fact that he had previously received gemtuzumab and platelets safely on separate days suggests that the gemtuzumab-platelet combination contributed to a fatal hypersensitivity reaction.

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In the era of precision medicine, the impact of personalized dosing of busulfan is not clear. We undertook a retrospective analysis of 78 patients with myeloid malignancies who received fludarabine and busulfan (FluBu4) with or without measuring Bu pharmacokinetics (Bu PK) and those who received busulfan with cyclophosphamide (BuCy). Fifty-five patients received FluBu4, of whom 21 had Bu PK measured, and 23 patients received BuCy. Total donor cell chimerism showed that the percentage of patients maintaining 100% donor chimerism on day 100 was 66.7%, 38.2%, and 73.9% in the FluBu4 with PK, FluBu4 with no PK, and BuCy, respectively (P = .001). Patients who had decreasing donor chimerism by day 100 were 23.8%, 52.9%, and 26.1% in the FluBu4 with PK, FluBu4 with no PK, and BuCy, respectively (P = .04). Bu PK group had fewer patients with less than 95% donor chimerism on day 30, which was not statistically significant, 5% (FluBu4 PK), 31% (FluBu4 with no PK), and 21% (BuCy) (P = .18). Survival distributions were not statistically significant (P = .11). Thus, personalized drug dosing can impact donor chimerism in myeloid malignancies. This will need to be examined in larger retrospective multicenter studies and prospective clinical trials.

have a worse prognosis despite having lower percentage of blasts in bone marrow or peripheral blood. This can be explained by what Walter et al reprted, using next-generation sequencing, that the proportion of neoplastic marrow cells is indistinguishable in MDS and secondary-AML even with myeloblast count of zero. HCT can be performed in those patients including older patients with promising results.

expansion was reliably achieved when artificial APCs were used. In contrast, when donor PBMCs (without artificial APCs) were used as the source of APCs, 10-100 fold fewer Tregs were obtained. Regardless of protocol, pTregs successfully prevented the proliferation of bead (CD2CD3CD28) stimulated self PBMCs with up to 50% suppression at a 1:32 ratio of Tregs:PBMCs. Contamination of CD8+ T cells was observed despite our efforts to gate out CD8 cells during sorting. Resorting of the Treg cultures early (day 14-21 post isolation) successfully eliminated the CD8s. Resorting inherently caused a significant loss of Tregs, leading to a longer culture period. Because Treg burnout was of concern, we assessed the function and phenotype of cells maintained in cultures >50 days and observed that Tregs with early high FoxP3 expression maintained function and phenotype. Finally, demonstration of fitness of cryopreserved pTregs is necessary for clinical application. Our preliminary studies show that Tregs can be re-cultured and re-expanded without loss of suppression or phenotype. In summary, we have successfully established several protocols for Treg expansion in the Cynomolgus macaque that can be used in pre-clinical studies of transplant tolerance induction.