Safety and Immunogenicity of the Live Attenuated Varicella Vaccine Following T Replete or T Cell-Depleted Related and Unrelated Allogeneic Hematopoietic Cell Transplantation (alloHCT)

There are limited studies assessing the live attenuated varicella vaccine following allogeneic hematopoietic cell transplantation (alloHCT). Because of the morbidity of varicella acquired after childhood, we immunized and retrospectively analyzed the safety and immunogenicity of this vaccine in 46 varicella zoster virus (VZV) seronegative patients <20 years old at HCT who achieved a CD4 cell count ≥200/μL, were off immunosuppression, and responded to ≥1 post-HCT vaccines. Two vaccinated patients lacking follow-up titers were excluded from analysis. Stem cells were derived from an HLA-matched sibling (n = 18) or an alternative (HLA mismatched related or unrelated) donor (n = 26). Median time to vaccination was 4 years. Sixty-four percent of patients seroconverted following 1 immunization. There was no significant difference in response between recipients of a matched related or alternative donor graft (P = .2) or between those given a T cell-depleted or T-replete alternative donor graft (P = .27). Three of 44 patients developed a self-limited varicella-like rash within 2.5 weeks of immunization. With a median follow-up of 29.1 (range: 6.9-167.1) months, there were no subsequent cases of varicella-like rashes. No patient developed shingles. This study suggests that this vaccine is safe and immunogenic when given according to preset clinical and immunologic milestones, warranting larger prospective studies in patients ≥24 months following HCT as outlined in current post-HCT vaccine guidelines

“No Wash” Albumin-Dextran Dilution for Double-Unit Cord Blood Transplantation is Safe with High Rates of Sustained Donor Engraftment

AbstractWashing cord blood (CB) grafts involves product manipulation and may result in cell loss. We investigated double-unit CB transplantation (CBT) using red blood cell (RBC)–depleted units diluted with albumin-dextran in patients with hematologic malignancies. One-hundred thirty-six patients (median age, 43 years; range, 4 to 71; median weight, 69 kilograms (kg); range, 24 to 111) underwent transplantation with a 4/6 to 6/6 HLA-matched graft. Patients ≤ 20 kg were excluded, as they only received washed units. Units were diluted a median of 8 fold to a median volume of 200 mL/unit. The median infused total nucleated cell doses were 2.7 (larger unit) and 2.0 (smaller unit) x 107/kg, respectively, and the median post-thaw recovery was 86%. Units were infused consecutively (median, 45 minutes/unit). While only 17 patients (13%) had no infusion reactions, reactions in the remaining 119 patients were almost exclusively mild-moderate (by CTCAE v4 criteria 12 grade 1, 43 grade 2, 63 grade 3) with only 1 patient (< 1%) having a severe (grade 4) reaction. Moreover, most were easily treated. Grade 2 to 3 hypertension was the most common in 101 (74%) patients. The cumulative incidence of sustained donor-derived neutrophil engraftment was high: 95% in myeloablative and 94% in nonmyeloablative CBT recipients. With appropriate supportive care, double-unit CBT with RBC-depleted grafts infused after albumin-dextran dilution is safe with high rates of engraftment in patients > 20 kg

Neonatal umbilical cord blood transplantation halts skeletal disease progression in the murine model of MPS-I

Umbilical cord blood (UCB) is a promising source of stem cells to use in early haematopoietic stem cell transplantation (HSCT) approaches for several genetic diseases that can be diagnosed at birth. Mucopolysaccharidosis type I (MPS-I) is a progressive multi-system disorder caused by deficiency of lysosomal enzyme α-L-iduronidase, and patients treated with allogeneic HSCT at the onset have improved outcome, suggesting to administer such therapy as early as possible. Given that the best characterized MPS-I murine model is an immunocompetent mouse, we here developed a transplantation system based on murine UCB. With the final aim of testing the therapeutic efficacy of UCB in MPS-I mice transplanted at birth, we first defined the features of murine UCB cells and demonstrated that they are capable of multi-lineage haematopoietic repopulation of myeloablated adult mice similarly to bone marrow cells. We then assessed the effectiveness of murine UCB cells transplantation in busulfan-conditioned newborn MPS-I mice. Twenty weeks after treatment, iduronidase activity was increased in visceral organs of MPS-I animals, glycosaminoglycans storage was reduced, and skeletal phenotype was ameliorated. This study explores a potential therapy for MPS-I at a very early stage in life and represents a novel model to test UCB-based transplantation approaches for various diseases