Long-Term Follow-Up of Abatacept, Post-Transplantation Cyclophosphamide, and Sirolimus-Based Haploidentical Transplantation in Younger Patients with Nonmalignant Diseases.

Haploidentical (haplo) hematopoietic cell transplantation (HCT) for nonmalignant disease (NMD) carries inherent challenges of both alloreactivity and graft failure. Building on promising results from pilot studies in which abatacept was combined with post-transplantation cyclophosphamide (PTCy) and sirolimus (AbaCyS) in younger NMD patients undergoing haplo-HCT, we present the long-term outcomes of this protocol. On the back of uniform disease-specific conditioning regimens containing antithymocyte globulin 4.

A Commoner at an Extremely Rare Site: A Case of Dorsal Intramedullary Spinal Dermoid Cyst.

Intramedullary dorsal dermoid cysts are rare benign tumors, arising from the nests of embryonic ectoderm, which get buried or trapped under the lines of fusion of the ectodermal folds in the developing embryo. We present a rare case of intramedullary dermoid cyst in a 30-year-old asymptomatic female, who presented with paraplegia and ataxia. Magnetic resonance imaging was suggestive of neoplastic intramedullary mass.

Intracranial Myopericytoma: A Rare Benign Tumor at an Extremely Rare Location.

A 50-year-old female presented with a history of seizures, headache, nausea, and vomiting. On imaging, parafalcine meningioma with mass effect features was rendered. She underwent right frontal tumor excision and craniotomy.

Intracranial Myopericytoma: A Rare Benign Tumor at an Extremely Rare Location.

A 50-year-old female with a history of seizures, headache, nausea, and vomiting. On imaging, parafalcine meningioma with mass effect features was rendered. She underwent right frontal tumor excision and craniotomy.

Early and Sustained Expansion of Adaptive Natural Killer Cells Following Haploidentical Transplantation and CTLA4Ig-Primed Donor Lymphocyte Infusions Dissociate Graft-versus-Leukemia and Graft-versus-Host Effects.

Background: Adaptive or memory natural killer (NK) cells with epigenetic imprints similar to memory T cells have been shown to develop in response to cytomegalovirus (CMV) infection with upregulation of activating receptor NKG2C. These cells have been shown to possess strong anti-tumour efficacy both in-vitro as well as in-vivo.

Objectives: To determine if reconstitution of adaptive NK cells (CD56NKG2CNKG2A) in patients with advanced leukemia undergoing haploidentical HCT had any impact on disease progression (DP).

CTLA4Ig-primed donor lymphocyte infusions following haploidentical transplantation improve outcome with a distinct pattern of early immune reconstitution as compared to conventional donor lymphocyte infusions in advanced hematological malignancies.

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.

CTLA4Ig in an Extended Schedule along with Sirolimus Improves Outcome with a Distinct Pattern of Immune Reconstitution Following Post-Transplantation Cyclophosphamide-Based Haploidentical Transplantation for Hemoglobinopathies.

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.

Prophylactic oseltamivir during major seasonal influenza H1N1 outbreak might reduce both H1N1 and associated pulmonary aspergillosis in children undergoing haploidentical transplantation.

Following a major seasonal outbreak of H1N1 influenza in 2018 September, prophylactic oseltamivir for six months was initiated in children undergoing haploidentical HCT with regular monitoring for influenza and other respiratory virus infections. Influenza was not detected in 22 children undergoing prophylaxis, compared to 8 H1N1 infections in 21 adults without prophylaxis (P = .01).

Alterations in NKG2A and NKG2C Subsets of Natural Killer Cells Following Epstein-Barr Virus Reactivation in CTLA4Ig-based Haploidentical Transplantation Is Associated With Increased Chronic Graft-Versus-Host Disease.

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.

CTLA4Ig-based reduced intensity conditioning and donor lymphocyte infusions for haploidentical transplantation in refractory aggressive B-cell lymphoma relapsing after an autograft: Early results from a pilot study.

CTLA4Ig-primed donor lymphocyte infusions (DLIs) have been found to promote natural killer (NK) cell-mediated anti-leukemia effect following haploidentical hematopoietic cell transplantation (HCT). Incorporation of CTLA4Ig in conditioning aided long-term remission in myeloma probably by blocking the CD28-CD86 pro-survival pathway when combined with CTLA4Ig-primed DLI. We explored a similar approach in 12 patients (8-65 years) who had refractory aggressive B-cell lymphoma (R-ABCL) following autologous HCT.

Allogeneic Hematopoietic Stem Cell Transplantation for Myeloma: Time for an Obituary or Not Just Yet!

The management of myeloma has evolved dramatically in the last two decades. High dose melphalan and autologous hematopoietic stem cell transplantation (HSCT) marked the beginning of this journey. This was followed by an explosion of novel agents which were approved for management of myeloma.

Rotavirus infection following post-transplantation cyclophosphamide based haploidentical hematopoietic cell transplantation in children is associated with hemophagocytic syndrome and high mortality.

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.

CTLA4Ig Primed Donor Lymphocyte Infusion: A Novel Approach to Immunotherapy after Haploidentical Transplantation for Advanced Leukemia.

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 .

Higher CD45RA Regulatory T Cells in the Graft Improves Outcome in Younger Patients Undergoing T Cell-Replete Haploidentical Transplantation: Where Donor Age Matters.

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.

Impact of Single-Dose Plerixafor as an Adjunct to Granulocyte Colony-Stimulating Factor-Based Peripheral Blood Stem Cell Mobilization on the Graft Composition and Outcome for T Cell-Replete Haploidentical Peripheral Blood Stem Cell Transplantation with Post-Transplantation Cyclophosphamide: A Comparative Study.

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 = .

T cell costimulation blockade promotes transplantation tolerance in combination with sirolimus and post-transplantation cyclophosphamide for haploidentical transplantation in children with severe aplastic anemia.

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.