Good Engraftment but Quality and Donor Concerns for Cryopreserved Hemopoietic Progenitor Cell Products Collected During the COVID-19 Pandemic.

Changes to donor availability, collection center capacity, and travel restrictions during the early phase of the COVID-19 pandemic led to routine cryopreservation of most unrelated donor products for hematopoietic transplantation prior to the recipient commencing the conditioning regimen. We investigated the effect of this change on unrelated donor product quality and clinical outcomes. Product information was requested from transplantation centers in Australia and New Zealand and clinical outcome data from the Australasian Bone Marrow Transplant Recipient Registry (ABMTRR). In total, 191 products were collected between April 1, 2021, and September 30, 2021, and most (74%) were from international collection centers. Median post-thaw CD34 recovery was 78% (range 25% to 176%) and median post-thaw CD34 viability was 87% (range 34% to 112%). Median time to neutrophil recovery was 17 days (interquartile range 10 to 24 days), and graft failure occurred in 6 patients (4%). These clinical outcomes were similar to those of "fresh" unrelated donor transplants reported to the ABMTRR in 2019. However, recipient transplantation centers reported problems with 29% of products in the form of damage during transit, low cell dose, inadequate labeling, missing representative samples, or missing documentation. These problems were critical in 7 cases (4%). At last follow-up, 22 products (12%) had not been infused. Routine cryopreservation of unrelated donor hemopoietic progenitor cell products has enabled safe continuation of allogeneic transplant services during the COVID-19 pandemic. However, practices for product tracing, documentation, and transportation can be optimized, and measures to reduce the incidence of unused unrelated donor product are required.

Pregnancy post autologous stem cell transplant with BEAM conditioning for multiple sclerosis.

BACKGROUND: Given the increasing numbers of multiple sclerosis (MS) patients undergoing autologous haematopoietic stem cell transplant (AHSCT) worldwide, and with women of childbearing age overrepresented in the target population, it is increasingly important to review fertility and pregnancy outcomes following AHSCT. OBJECTIVE: To evaluate the rate of pregnancy and complications post-AHSCT for MS. METHOD: Retrospective evaluation of the rate of pregnancy and associated complications in a cohort of patients post-AHSCT with BEAM conditioning for MS since 2010 in a tertiary referral centre. RESULTS: In our ongoing Phase 2 trial of AHSCT for MS, 55 patients have undergone AHSCT with 30 females being of childbearing age at time of transplantation. Four pregnancies occurred following AHSCT. Two pregnancies were carried to term. No maternal or neonatal complications were reported in either case. Two pregnancies were not carried to term due to elective terminations. Both of these patients became pregnant unexpectedly 2 years following AHSCT. Of the 21 male patients, one patient has fathered three children since his AHSCT. There were no newborn complications. CONCLUSIONS: This is the first report to our knowledge on fertility outcomes in both sexes post-AHSCT for MS. Patients of both sexes should be counselled prior to treatment on infertility and contraceptive use.

miR-10a is aberrantly overexpressed in Nucleophosmin1 mutated acute myeloid leukaemia and its suppression induces cell death.

BACKGROUND: Acute myeloid leukaemia (AML) with nucleophosmin-1 (NPM1) mutation is a major subtype of AML. The NPM1 mutation induces a myeloproliferative disorder, but evidence indicates that other insults are necessary for the development of AML. We utilised microRNA microarrays and functional assays to determine if microRNA dysregulation could be involved in the pathogenesis of in NPM1 mutated (NPM1mut)-AML. RESULTS: We used a stringent locked nucleic acid (LNA) based microRNA microarray platform to profile bone marrow samples of patients with normal karyotype AML. A panel of five microRNAs dichotomised AML patients according to their NPM1 mutational status. miR-10a, let-7b and let-7c were significantly over-expressed, while miR-130a and miR-335 were under-expressed in NPM1mut-AML when compared to NPM1wildtype-AML. Of these, miR-10a is the most differentially expressed in NPM1mut-AML versus NPM1wildtype-AML (> 10 fold higher as confirmed by qRT-PCR). To investigate the functions of miR-10a, the OCI-AML3 cell line was utilised, which is the only commercially available cell line bearing NPM1mut. OCI-AML3 cells were firstly demonstrated to have a similarly high miR-10a expression to primary NPM1mut-AML patient samples. Inhibition of miR-10a expression by miRCURY LNA Inhibitors (Exiqon) in these cells resulted in increased cell death as assessed by MTS, cell cycle and Annexin-V assays and reduced clonogenic capacity, indicative of an involvement in leukaemic cell survival. In silico filtering of bioinformatically predicted targets of miR-10a identified a number of potential mRNA targets with annotated functions in haematopoiesis, cell growth and apoptosis. Lucferase reporter assays confirmed a number of these putative tumorogenic genes that are miR-10a suppressible including KLF4 and RB1CC1. This provides a potential mechanism for the pathogenic role of miR-10a in NPM1mut-AML. CONCLUSIONS: This study provides, for the first time, in vitro evidence of a pro-survival role of miR-10a in NPM1mut-AML, that it may contribute to the pathogenesis of NPM1mut-AML and identifies putative tumorogenic targets.