Cord blood transplants supported by unrelated donor CD34(+)progenitor cells
BONE MARROW TRANSPLANTATION
Authors: Gomez-Arteaga, Alexandra; Orfali, Nina; Guarneri, Danielle; Cushing, Melissa M.; Gergis, Usama; Hsu, Jingmei; Hsu, Yen-Michael S.; Mayer, Sebastian A.; Phillips, Adrienne A.; Chase, Stacy A.; Mokhtar, Asmaa E.; Shore, Tsiporah B.; Van Besien, Koen
Alternative donor transplantation with the haplo-cord platform allows the use of a lower-dose single umbilical cord blood unit (CBU) by co-infusion of third-party CD34(+)-selected cells from a haploidentical relative, which provides early transient engraftment while awaiting durable CBU engraftment. In our experience, similar to 15% of patients lack a suitable haploidentical donor. Here we report 26 patients who underwent haplo-cord transplant using CD34(+)-selected partially matched unrelated donor grafts. Twenty-four were conditioned with fludarabine/melphalan +/- low-dose TBI (n = 16). Twenty-five received ATG and all received posttransplant tacrolimus and mycophenolate mofetil. Median time to neutrophil and platelet recovery was 11 and 18 days. CBU engraftment, with CD33 and CD3 >5% cord chimerism in the myeloid/lymphoid compartment by day +60, occurred in 20 of 24 patients (83%). Incidence of grade 2-4 acute graft-versus-host disease (GVHD) was 27% at day +100, and chronic GVHD was 4% at 1 year. Overall survival at 1 year was 54%. For patients in need of an alternative transplant who lack a haploidentical donor, haplo-cord transplantation using CD34(+)-selected partially matched unrelated donor grafts results in rapid engraftment with no increased rate of cord graft failure or GVHD.
Immunophenotypic dysplasia and aberrant T-cell antigen expression in acute myeloid leukaemia with complex karyotype and TP53 mutations
JOURNAL OF CLINICAL PATHOLOGY
Authors: Dannheim, Katelyn C.; Pozdnyakova, Olga; Dal Cin, Paola; Weinberg, Olga K.
Aims Cytogenetic and molecular aberrations are the strongest factors in determining outcome in acute myeloid leukaemia (AML). AML with complex karyotype confers a particularly poor prognosis and is associated with morphologic dysplasia. Flow cytometric immunophenotyping (FCI) has been investigated in defining dysplasia within myelodysplastic syndromes, but little is known about immunophenotypic dysplasia in AML and correlation with genetic abnormalities. This study aimed to explore differences in antigen expression by FCI in AML with complex karyotype (AML-CK) and AML with complex karyotype and TP53 mutations (AML-TP53) compared with AML with normal karyotype (AML-NK). Methods Twenty-five cases of AML-CK, 13 of which had abnormalities of TP53, were compared with 83 cases of AML-NK using FCI. Results Our findings demonstrated brighter expression of CD34 with decreased CD33 and aberrant expression of CD5 in blasts of AML-CK, while AML-TP53 blasts exhibited brighter expression of CD13. Granulocytes in AML-CK exhibited brighter expression of CD5, CD7, CD10 and CD14, with brighter CD3 also seen in AML-TP53. Conclusions Our results suggest that immunophenotypic dysplasia correlates with complex karyotype and TP53 mutation, including increased expression of T-cell antigens.