Post infusion CY

The use of human leukocyte antigen (HLA)-haploidentical haematopoietic stem cell transplantation (HSCT) with post-transplant cyclophosphamide (PTCY), which markedly reduces the risk of graft-versus-host disease, has rapidly increased worldwide, even in children. It was initially developed for post-transplant relapse or non-remission at transplant for patients with high-risk haematologic malignancies. However, this strategy is currently used more frequently for standard-risk, transplant-eligible paediatric haematological malignancies...

HLA-haploidentical stem cell transplantation (haplo-SCT) using post-transplant high-dose cyclophosphamide (PT-CY) is an alternative choice when a suitable donors is unavailable. However, PT-CY is difficult in patients with Fanconi anemia (FA) due to their high vulnerability to alkylating agents. For FA, we prefer haplo-SCT by T-cell receptor αβT-cell and B-cell depletion (αβT/B-depleted haplo-SCT), which can reduce the risks of PT-CY-related complications and graft-versus-host disease (GVHD)...

PURPOSE: Hematopoietic cell transplantation (HCT) has curative potential for myeloid malignancies, though many patients cannot tolerate myeloablative conditioning with high-dose chemotherapy alone or with total-body irradiation (TBI). Here we report long-term outcomes from a phase 1/2 study using iodine-131 (131I)-anti-CD45 antibody BC8 combined with nonmyeloablative conditioning prior to HLA-haploidentical HCT in adults with high-risk relapsed/ refractory acute myeloid or lymphoid leukemia (AML and ALL), or myelodysplastic syndrome (MDS) [ClinicalTrials...

OBJECTIVE: Relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a serious life-threatening complication. The granulocyte colony-stimulated factor mobilized donor lymphocyte infusions (gDLI) combined with chemotherapy is currently a commonly used treatment method. Nevertheless, gDLI may cause so severe acute graft-versus-host disease (aGVHD) as to impact prognosis. Posttransplant cyclophosphamide (PTCy) has been the backbone for GVHD prophylaxis by inducing tolerance to minor histocompatibility antigens in recipients, while the application of post-gDLI low-dose cyclophosphamide (PDCy) for GVHD prophylaxis has not yet been attempted...

Patients receiving autologous chimeric antigen receptor T cell (CAR-T) therapy for multiple myeloma (MM) may require bridging therapy (BT) before CAR-T infusion to maintain some level of disease control. Alkylators, such as cyclophosphamide (Cy), are often used in regimens, either in high-intensity regimens, such as modified hyperCVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone), or once-weekly regimens, such as KCd (carfilzomib, cyclophosphamide, and dexamethasone). However, there is no consensus regarding the optimal BT alkylator dose intensity in MM...

CONTEXT: The use of post-transplant cyclophosphamide (PT-Cy) has favored haploidentical hematopoietic stem cell transplantation (haplo-HSCT) when an HLA-matched donor is not available or when an urgent transplant is needed. Although a high percentage of patients receiving PT-Cy haplo-HSCT develop cytokine release syndrome (CRS) after infusion, it only seems to affect prognosis in the reduced proportion of patients that develop severe CRS. Literature regarding the clinical impact of this complication is scarce...

CONTEXT: Fludarabine followed by fractionated total body irradiation (Flu/FTBI) as conditioning was well-studied in allo-HSCT. Cyclophosphamide as pre-FTBI (Cy/FTBI) and post-FTBI (FTBI/Cy) has also shown acceptable outcomes, although data are limited. However, unlike FTBI/Cy, no studies have examined FTBI followed by fludarabine (FTBI/Flu). Due to logistics, we have used FTBI/Flu or FTBI/Cy with appropriate stem cell infusion timing. OBJECTIVE: Report outcomes using FTBI/Flu and FTBI/Cy conditioning...

Biomarker-guided dosing may improve the efficacy and toxicity of cyclophosphamide (CY); however, clinical studies evaluating their association with the area under the plasma concentration curve (AUC) of CY and its metabolites are time- and resource-intensive. Therefore, we sought to identify lipidomic biomarkers associated with the time-varying differences in CY formation clearance to 4-hydroxycyclophosphamide (4HCY), the principal precursor to CY's cytotoxic metabolite. Hematopoietic cell transplant (HCT) patients receiving post-transplant CY (PT-CY) were enrolled, cohort 1 (n=25) and cohort 2 (n=26) donating longitudinal blood samples before they started HCT (pre-HCT), before infusion of the donor allograft (pre-graft), before the first dose of PT-CY (pre-CY) and 24 hours after the first dose of PT-CY (24-h post-CY) which is also immediately before the second dose of CY...

Our study examined renal function change in older adults with osteoporosis, treated with zoledronic acid. Risk of nephrotoxicity was low. Future studies are needed to evaluate use of zoledronic acid in patients with a CCr < 35 mL/min, as patients may be inappropriately excluded from its use. INTRODUCTION: Zoledronic acid (ZA) is used for the treatment of osteoporosis (OP). Renal impairment is a known risk factor for the rare occurrence of nephrotoxicity after ZA infusions, leading to use being contraindicated below creatinine clearance (CCr) of 35 mL/min...

The widely used alkylating agent cyclophosphamide (CY) has substantive interpatient variability in the area under the curve (AUC) of it and its metabolites. Numerous factors may influence the drug-metabolizing enzymes that metabolize CY to 4-hydroxycyclophosphamide (4HCY), the principal precursor to CY's cytotoxic metabolite. We sought to identify endogenous metabolomics compounds (EMC) associated with 4HCY formation clearance (ratio of 4HCY/CY AUC) using global metabolomics. Hematopoietic cell transplant (HCT) patients receiving post-transplant CY (PT-CY) were enrolled, cohort 1 (n=26) and cohort 2 (n=25) donating longitudinal blood samples before they started HCT (pre-HCT), before infusion of the donor allograft (pre-graft), before the first dose of PT-CY (pre-CY), and 24 hours after the first dose of PT-CY (24-hr post-CY) which is also immediately before the second dose of CY...

Severe aplastic anemia II (SAA-II) progresses from non-severe aplastic anemia (NSAA). The unavailability of efficacious treatment has prompted the need for haploidentical bone marrow transplantation (haplo-BMT) in patients lacking a human leukocyte antigen (HLA)-matched donor. This study aimed to investigate the efficacy of haplo-BMT for patients with SAA-II. Twenty-two patients were included and followed up, and FLU/BU/CY/ATG was used as conditioning regimen. Among these patients, 21 were successfully engrafted, 19 of whom survived after haplo-BMT...

G-CSF only mobilisation has been shown to enhance immune reconstitution early post-transplant, but its impact on survival remains uncertain. We undertook a retrospective review of 12 transplant centres to examine overall survival (OS) and time to next treatment (TTNT) following melphalan autograft according to mobilisation method (G-CSF only vs. G-CSF and cyclophosphamide [CY]) in myeloma patients uniformly treated with bortezomib, cyclophosphamide and dexamethasone induction. Six centres had a policy to use G-CSF alone and six to use G-CSF + CY...

Cytokine release syndrome (CRS), occurring in more than 70% of HLA-haploidentical hematopoietic stem-cell transplantations with post-transplant cyclophosphamide (PT/CY-haplo), can lead to hemodynamic instability and worsen clinical outcomes. A calcineurin inhibitor is initiated after cyclophosphamide administration in the commonly used PT/CY regimens. Here, we conducted a phase I/II, prospective, single-center trial of PT/CY-haplo to evaluate the safety and efficacy of cyclophosphamide on days 3 and 5 along with cyclosporin and mycophenolate mofetil started from day - 1...

Allogeneic hematopoietic stem cell transplantation is curative for transfusion-dependent thalassemia, but mixed chimerism (MC) may herald graft rejection. We report a child who failed bone marrow transplant (BMT) from matched unrelated donor (MUD) successfully salvaged with haploidentical peripheral blood stem cell transplant (PBSCT), but had MC in T-lymphocyte compartment despite near-complete donor chimerism in myeloid compartment. MC was successfully improved by repeated CD45RA-depleted donor lymphocyte infusion (DLI)...

The use of cyclophosphamide (CY) for bidirectional tolerization of recipient and donor T cells is associated with reduced rates of graft-versus-host disease (GVHD) and nonrelapse mortality (NRM) after HLA-matched hematopoietic stem cell transplantation (HSCT). However, recurrent disease remains the primary barrier to long-term survival. We extended our 2-step approach to HLA-matched related HSCT using a radiation-based myeloablative conditioning regimen combined with a high dose of T cells in an attempt to reduce relapse rates while maintaining the beneficial effects of CY tolerization...

Hemorrhagic cystitis (HC) is an important complication after haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with post-transplantation cyclophosphamide (PT-CY). Sodium 2-mercaptoethanesulfonate (MESNA) can prevent bladder injury when given with PT-CY. However, the best way to deliver MESNA is not known. This study assessed the incidence of HC after haplo-HSCT with PT-CY with 2 different methods of MESNA administration. The cumulative incidence of HC was lower in patients who received MESNA as a continuous infusion compared with those who received it as an intermittent bolus (5...

HLA-haploidentical allogeneic hematopoietic cell transplantation (allo-HCT) using post-transplantation cyclophosphamide (PT/Cy-haplo) is becoming the standard of care for patients without HLA-matched related or unrelated donors. PT/Cy-haplo could provide more patients the opportunity to receive allo-HCT, since most patients have more than one available HLA-haploidentical related donor candidate. In PT/Cy-haplo settings, however, an optimal donor selection algorithm has not yet been established. To contribute to the establishment of a donor selection formula based on disease status and killer-cell immunoglobulin-like receptor (KIR) genotype, we retrospectively analyzed 91 patients who received PT/Cy-haplo at our institute...

Haploidentical hematopoietic stem cell transplantation (haploHSCT) with conditioning regimens using post-transplant cyclophosphamide (PTCy) for peripheral blood stem cell (PBSC) grafts is limited by comparably higher rates of acute and chronic graft-versus-host disease (GVHD). Antithymocyte globulin (ATG) may mitigate this risk. We evaluated haploHSCT after reduced-intensity conditioning (RIC) with ATG, PTCy, and cyclosporine to prevent rejection and GVHD. Fifty adults underwent haploHSCT from August 2016 to February 2018...

OBJECTIVE: To study the impact of the C-peptide and beta-cell autoantibody testing required by the Center for Medicare and Medicaid Services (CMS) on costs/utilization for patients with diabetes mellitus initiating continuous subcutaneous insulin infusion (CSII) therapy. METHODS: This retrospective study used propensity score-matched patients. Analysis 1 compared patients 1-year pre- and 2-years post-CSII adoption who met or did not meet CMS criteria. Analysis 2 compared Medicare Advantage patients using CSII or multiple daily injections (MDI) who did not meet CMS criteria for 1-year pre- and 1-year post-CSII adoption...

The use of posttransplant cyclophosphamide (PT-Cy) as graft-versus-host disease (GVHD) prophylaxis has revolutionized haploidentical hematopoietic stem cell transplantation (HSCT), allowing safe infusion of unmanipulated T cell-replete grafts. PT-Cy selectively eliminates proliferating alloreactive T cells, but whether and how it affects natural killer (NK) cells and their alloreactivity is largely unknown. Here we characterized NK cell dynamics in 17 patients who received unmanipulated haploidentical grafts, containing high numbers of mature NK cells, according to PT-Cy-based protocols in 2 independent centers...