High rates of MHC mismatches in HLA matched unrelated donor/recipient pairs and potential impact on hematopoietic cell transplant outcome.

Introduction: Donors for patients requiring hematopoietic cell transplant (HCT) are selected based on matching genetic sequences encoding the antigen recognition domain of specific HLA loci. However, differences in transplant outcomes in fully matched unrelated HCT compared with sibling HCT suggest that other genetic regions within the major histocompatibility complex (MHC) may contribute to HCT outcomes.

Methods: We sequenced the non-classical MHC loci (NCML) HLA-E, -F, -G, -H, MICA and MICB on a well-characterized retrospective cohort of 157 unrelated donor/recipient HCT pairs to determine the extent of MHC mismatching in matched pairs.

Severity and organ distribution of chronic graft-versus-host disease with posttransplant cyclophosphamide-based versus methotrexate/calcineurin inhibitor-based allogeneic hematopoietic cell transplantation.

The reduced risk of chronic graft-versus-host-disease (GVHD) with posttransplant cyclophosphamide (ptCy) in the setting of haploidentical related donor and more recently, with HLA-matched related and matched and mismatched unrelated donor allogeneic transplantation has been established. There is, however, paucity of data to show if ptCy impacts chronic GVHD pathogenesis, its phenotype and evolution after HCT regardless of the donor status. We examined the differences in chronic GVHD incidence and presentation in 314 consecutive patients after receiving their first allogeneic transplantation (HCT) using ptCy-based GVHD prophylaxis (ptCy-HCT; n = 120; including 95 with haploidentical related donor) versus conventional calcineurin inhibitor-based prophylaxis (CNI-MUD; n = 194) between 2012 and 2019.

Stem Cell Mobilization Yields with Daratumumab- and Lenalidomide-Containing Quadruplet Induction Therapy in Newly Diagnosed Multiple Myeloma: Findings from the MASTER and GRIFFIN Trials.

For eligible patients with newly diagnosed multiple myeloma (NDMM), standard of care includes induction therapy followed by autologous stem cell transplantation (ASCT). Daratumumab as monotherapy and in combination treatment is approved across multiple lines of therapy for multiple myeloma (MM), and lenalidomide is an effective and commonly used agent for induction and maintenance therapy in MM. However, there is concern that lenalidomide and daratumumab given as induction therapy might impair mobilization of stem cells for ASCT.

Propylene Glycol-Free Melphalan versus PG-Melphalan as Conditioning for Autologous Hematopoietic Cell Transplantation for Myeloma.

High-dose melphalan (Mel) conditioning before autologous hematopoietic cell transplantation (autoHCT) is standard of care for patients with transplantation-eligible multiple myeloma. The traditional lyophilized Mel formulation has inadequate solubility and stability after reconstitution, leading to the use of propylene glycol (PG) as a solubilizing agent. A newer PG-free Mel preparation (Evomela) uses beta cyclodextrin captisol as a solubilizing agent and was approved by the United States Food and Drug Administration as a conditioning agent based on a single-phase IIb study showing bioequivalence.

Utilization and Cost Implications of Hematopoietic Progenitor Cells Stored for a Future Salvage Autologous Transplantation or Stem Cell Boost in Myeloma Patients.

Autologous hematopoietic cell transplantation (autoHCT) is a standard initial treatment for multiple myeloma (MM). Consensus guidelines recommend collecting sufficient hematopoietic progenitor cells (HPCs) for 2 autoHCTs in all eligible patients. Despite a lack of published data on the utilization of HPCs stored for future use, it is common practice across transplantation programs to collect enough HPCs for 2 autoHCTs in MM patients.

Ixazomib for Chronic Graft-versus-Host Disease Prophylaxis following Allogeneic Hematopoietic Cell Transplantation.

Chronic graft-versus-host disease (cGVHD) is major cause of morbidity and mortality following allogeneic hematopoietic cell transplantation (HCT). Ixazomib is an oral, second-generation, proteasome inhibitor that has been shown in preclinical models to prevent GVHD. We conducted a phase I/II trial in 57 patients to evaluate the safety and efficacy of ixazomib administration for cGVHD prophylaxis in patients undergoing allogeneic HCT.

Severity of Cytokine Release Syndrome and Its Association with Infections after T Cell-Replete Haploidentical Related Donor Transplantation.

An increased risk of infections has been described after T cell-replete haploidentical cell transplantation (haploHCT). Cytokine release syndrome (CRS) after haploHCT is a known phenomenon, but the impact of CRS severity on the risk of infections remains unexplored. We retrospectively evaluated 78 consecutive adult haploHCT recipients from 2012 to 2018 for the development of CRS (graded based on the criteria of Lee et al) and examined the incidence and mortality due to infections in correlation with CRS severity.

Fludarabine/Busulfan Conditioning-Based Allogeneic Hematopoietic Cell Transplantation for Myelofibrosis: Role of Ruxolitinib in Improving Survival Outcomes.

Allogeneic hematopoietic cell transplantation (allo-HCT) is the only curative treatment modality for primary myelofibrosis (MF) and related myeloproliferative neoplasms. Older age at diagnosis and age-related comorbidities make most patients ineligible for allo-HCT, given concerns for nonrelapse mortality (NRM). Here we report the outcomes of 37 consecutive recipients of allo-HCT for MF performed at a single center between 2009 and 2018 with a standardized institutional protocol.

Lifitegrast ophthalmic solution for treatment of ocular chronic graft-versus-host disease.

Ocular chronic graft-versus-host disease (oGVHD) is a relatively common complication that occurs following allogeneic hematopoietic cell transplantation. Keratoconjunctivitis sicca (KCS) is the most common manifestation of oGVHD. Lifitegrast is a lymphocyte function-associated antigen-1 antagonist approved to reduce inflammation and symptoms in patients with dry eye disease.

Incidence and characteristics of engraftment syndrome after autologous hematopoietic cell transplantation in light chain amyloidosis.

Engraftment syndrome (ES), a complication of autologous hematopoietic cell transplantation (auto-HCT), can occur around the time of neutrophil recovery. We sought to identify the incidence of ES in light chain (AL) amyloidosis patients undergoing auto-HCT at our centre by evaluating 72 consecutive amyloidosis patients transplanted between 1999 and 2017. To assess trends in ES over time, patients were divided into two Eras (Era 1 = 1999-2008 and Era 2 = 2009-2017) based on year of auto-HCT.

Direct HLA Genetic Comparisons Identify Highly Matched Unrelated Donor-Recipient Pairs with Improved Transplantation Outcome.

HLA matching by allele-level genotyping is largely based on genetic similarity between a few exons that encode the antigen recognition domain (ARD) of the HLA protein. Next-generation sequencing (NGS) can identify HLA genetic polymorphisms in non-ARD-encoding exons, introns, and untranslated regions, but the impact of these polymorphisms on hematopoietic cell transplantation (HCT) outcome is unclear. We performed NGS-based sequencing of 11 HLA loci on a well-characterized retrospective cohort of 166 unrelated donor-recipient HCT pairs.

Bortezomib-induced Severe Congestive Heart Failure.

The clinical manifestations of anti-cancer drug associated cardiac side effects are diverse and can range from acutely induced cardiac arrhythmias to severe contractile dysfunction, and potentially fatal heart failure. Anthracyclines and trastuzumab cardiac toxicity have been well described and left ventricular ejection fraction (LVEF) evaluation is commonly performed before their use. Bortezomib (Velcade), a potent, specific and reversible proteasome inhibitor is approved for treatment of multiple myeloma (MM).