Publications by authors named "Prakash Bhakuni"

Direct Acting Antivirals (DAA) have changed the landscape of hepatitis C virus (HCV) infection with high cure rates across genotypes. However, the use of these agents in the setting of allogeneic hematopoietic cell transplantation (HCT) has been limited. In this context, we report the outcome of five children (5-12 years) with relapsed and refractory leukemia and active HCV infection (genotype 1b), who underwent urgent haploidentical HCT and were treated with Sofosbuvir and Velpatasvir (Sof-Vel) from initiation of treatment to 24 weeks post-HCT.

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CTLA4Ig has a unique property to spare or even potentiate natural killer (NK) cell-mediated cytotoxicity, whilst inhibiting T cell activation. We explored the efficacy of prophylactic DLI following CTLA4Ig (CTLA4Ig-DLI group, n = 75), compared to conventional DLI (DLI group, n = 50), in patients with advanced hematological malignancies receiving PTCy-based haploidentical transplantation. Acute and chronic GVHD in the CTLA4Ig-DLI group were 9.

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The major hindrances to the success of a haploidentical hematopoietic cell transplantation for hemoglobinopathies are graft failure, early post-transplant hemophagocytic syndrome (PTHPS), and graft-versus-host disease (GVHD). Following the successful incorporation of CTLA4Ig (abatacept) in post-transplantation cyclophosphamide-based haploidentical transplantation, we piloted this approach in 10 patients (aged 3 to 19 years), with thalassemia major (TM, n=5) and sickle cell disease (n = 5). Pretransplant immunosuppressive therapy (pTIST) was administered for 10 weeks.

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Background: The impact of newer approaches to haploidentical transplantation on Epstein-Barr virus (EBV) is largely unknown.

Methods: We prospectively evaluated the incidence of EBV reactivation and its impact on transplantation outcomes in 71 patients undergoing haploidentical transplantation with posttransplantation cyclophosphamide in combination with CTLA4Ig-based T-costimulation blockade.

Results: Eight patients developed EBV reactivation at a median of 96 days with no incidence of lymphoproliferative disorder.

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We evaluated the incidences and consequences of rotavirus induced diarrhea in a cohort of 115 patients undergoing T-cell replete haploidentical transplantation. Four out of 115 patients developed rotavirus-induced diarrhea between 47 and 147 days. The incidence of rotavirus infection was 9.

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We prospectively studied the impact of preemptive granulocyte infusions (pGIs) in 69 patients colonized with carbapenem-resistant gram-negative bacteria (CRGNB) undergoing haploidentical hematopoietic cell transplantation (HCT) compared with a previous cohort of 33 patients who received only antimicrobials directed toward CRGNB at the onset of neutropenic fever (non-pGI group). All patients developed neutropenic fever at a median of day +8 (range, -4 to +12) after transplantation. Engraftment kinetics were similar for both groups.

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CTLA4Ig attenuates T cell activation by co-stimulation blockade, but natural killer (NK) cells are not only resistant to CTLA4Ig, they also may demonstrate better antileukemia effect in the presence of CTLA4Ig. To explore this phenomenon we used sequential CTLA4Ig primed donor lymphocyte infusion (DLI) after post-transplant cyclophosphamide-based haploidentical transplantation. Thirty patients (CTLA4Ig-DLI group) with advanced leukemia received CTLA4Ig on day -1 and subsequently on days +7, +21, and +35, followed 12hours later by DLI of 1 to 10 × 10 CD3 T cells/kg containing .

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To understand the phenomenon of early alloreactivity (EA) in younger children undergoing post-transplantation cyclophosphamide (PTCy)-based haploidentical transplantation, we studied the graft composition and the immune reconstitution in 32 consecutive patients (aged 2 to 25 years) undergoing PTCy and T cell costimulation blockade based peripheral blood stem cell transplantation with emphasis on CD45RA subset of regulatory T cells (Tregs). All but 1 engrafted, and 14 patients experienced EA (acute graft-versus-host disease grades II to IV, n = 8; and post-transplantation hemophagocytic syndrome, n = 6) with a cumulative incidence of 43.7%; 42% developed mild chronic graft-versus-host disease.

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We conducted a prospective study on T and natural killer (NK) cell subset composition of graft and transplant outcomes in T cell-replete haploidentical transplantation with a single dose of subcutaneous plerixafor (Px) added to granulocyte colony-stimulating factor (G-CSF)-based mobilization in allogeneic donors to collect 10 × 10/kg CD34 hematopoietic stem cells (HSCs) at single apheresis. Twnety-six donors received G-CSF + Px and 25 G-CSF alone for mobilization. Despite significantly lower peripheral blood (PB) CD34 HSCs on day 4 in the G-CSF + Px group (33 [range, 6-47] cells/µL versus 81 [range, 50-168] cells/µL in the G-CSF group; P = .

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We conducted a pilot study employing extended T cell costimulation blockade (COSBL) with Abatacept along with sirolimus and post-transplantation cyclophosphamide (PTCy) in 10 patients (median age 12) with severe aplastic anemia (SAA). Nine patients engrafted in the COSBL group, compared to all 10 patients (median 14 vs 13days) treated on PTCy protocols without abatacept (CONTROL group). The incidence of acute graft-versus-host disease (GVHD) was 10.

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We conducted a pilot study on the feasibility of CD56-enriched donor cell infusion after post-transplantation cyclophosphamide (PTCy) for 10 patients with advanced myeloid malignancies undergoing haploidentical peripheral blood stem cell transplantation with cyclosporine alone as graft-versus-host disease (GVHD) prophylaxis and compared the outcome and immune reconstitution with a control group of 20 patients undergoing the same without CD56-enriched donor cell infusion. An early and rapid surge of mature NK cells as well as CD4 T cells and regulatory T cells (Tregs) was noted compared with the control group. KIR of donor phenotype reconstituted as early as day 30 with expression of CD56CD16NKG2AKIR phenotype.

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