Allogeneic transplant in myeloma

Graft-vs-host disease (GVHD) of the gastrointestinal (GI) tract is notably a serious complication of allogeneic hematopoietic stem cell transplant (HSCT). However, GI GVHD has rarely been reported in autologous HSCT, and the pathophysiology remains unclear. Diagnosing GVHD after autologous HSCT requires a high level of clinical suspicion, given its nonspecific clinical presentation and endoscopic findings necessitating a histological diagnosis for confirmation. We present a case of autologous GVHD involving the GI tract in a patient with multiple myeloma who responded well to corticosteroids, highlighting the importance of early identification of this rare entity to initiate therapy and improve outcomes...

OBJECTIVES: The seroprevalence of antibodies against Cytomegalovirus (CMV) is an established poor prognostic factor for patients receiving an allogeneic stem cell transplantation. However, the impact of CMV serology on outcome after autologous stem cell transplantation remains unknown. METHODS: Here, we analyzed the CMV immunoglobulin (Ig) serology of 446 newly-diagnosed multiple myeloma (MM) patients of the GMMG-MM5 phase III trial with a median follow-up of 58 months...

BACKGROUND: Maintenance after allogeneic hematopoietic cell transplantation (alloHCT) with hypomethylating agents has yielded conflicting results. MATERIALS AND METHODS: We conducted a single center retrospective matched-control analysis with the study group (5-azacitidine [AZA] group) including adults with FLT3-negative acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) who received post-transplant AZA maintenance off clinical trial (n = 93). A matched control group was comprised of contemporaneous AML/MDS patients who did not receive any maintenance (n = 357)...

BACKGROUND: The optimal timing of vaccination with SARS-CoV-2 vaccines after cellular therapy is incompletely understood. OBJECTIVE: To describe humoral and cellular responses after SARS-CoV-2 vaccination initiated <4 months versus 4-12 months after cellular therapy. DESIGN: Multicenter prospective observational study. SETTING: 34 centers in the United States. PARTICIPANTS: 466 allogeneic hematopoietic cell transplant (HCT; n=231), autologous HCT (n=170), or chimeric antigen receptor T cell (CAR-T cell) therapy (n=65) recipients enrolled between April 2021 and June 2022...

Allogeneic hematopoietic stem cell transplantation (AHSCT) is an important modality in the treatment of acute leukemia and other hematologic disorders. The post-transplant period is associated with prolonged periods of impaired immune function. Delayed T-cell immune reconstitution is correlated with increased risk of viral, bacterial, and fungal infections. This risk increases with high intensity inductions regimens often required for alternative donor sources. Current therapies for prophylaxis and treatment of these infections are limited by poor efficacy and significant toxicity...

Introduction Blood cancer survivors are at increased risk for medical complications. Methods Our questionnaire-based study involved 1,551 blood cancer survivors with a ≥3-year interval since the last intense treatment. Its goal was to quantify health-related complications during follow-up and assess their impact on the patients' lives. Results 20.4% of responding survivors reported a disease relapse, most often in indolent lymphomas. Second primary malignancies occurred in 14.1%, primarily in lymphoma and allogeneic transplantation survivors...

Antibody-based immunotherapies have revolutionized leukemia and lymphoma treatment, with animal studies being crucial in evaluating effectiveness and side effects. By targeting the evolutionary conserved Slamf7 immune receptor, which is naturally expressed by the murine multiple myeloma cell line MPC-11, we have developed a syngeneic mouse model for direct comparison of three immunotherapies: monoclonal antibodies (mAb), bispecific T cell engagers (BiTE), and CAR T cells (CART), all targeting Slamf7. Slamf7-BiTE is a bispecific single-chain antibody consisting of α-Slamf7 and α-CD3 Fv fragments joined through a Gly-Ser linker, and Slamf7-CART comprises the α-Slamf7 Fv fragment fused to the msCD8α transmembrane and msCD28, 4-1BB and CD3ζ intracellular signaling domains...

The integration of immune and targeted therapies into the treatment of acute lymphoblastic leukemia (ALL) has significantly improved outcomes, reduced the intensity and duration of chemotherapy, and the reliance on allogeneic stem cell transplantation (SCT). In younger patients with Philadelphia chromosome (Ph)-negative ALL, treatment with Hyper-CVAD and blinatumomab +/- inotuzumab has improved the 3-year overall survival (OS) to above 85%. In older patients, using less intensive chemotherapy (mini-Hyper-CVD) in combination with inotuzumab and blinatumomab has improved the 5-year OS rate to 50%...

The outcome of Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) has improved significantly following the introduction of the BCR::ABL1 tyrosine kinase inhibitors (TKIs). The addition of newer-generation and more potent TKIs resulted in higher rates of molecular responses and better survival. Achieving a complete molecular remission (CMR; disappearance of the BCR::ABL1 transcripts) within the first 3 months of therapy is an important endpoint in newly diagnosed Ph-positive ALL that identifies patients who have an excellent long-term survival and who may not need to receive an allogeneic hematopoietic stem cell transplantation (HSCT) in first complete remission (CR)...

BACKGROUND: Acute lymphoblastic leukemia represents 20% of acute leukemias in adults. Currently, there is limited data in Chile regarding the clinical, cytogenetic, and prognostic characteristics of this condition. METHODS: This is a retrospective, observational, and descriptive study of 67 patients treated for acute lymphoblastic leukemia at the Arturo Lopez Perez Foundation between 2018 and 2021. The main objective is to evaluate epidemiological and clinical characteristics, as well as identifying factors associated with improved overall survival and/or progression-free survival...

BACKGROUND: The quality and quantity of hematopoietic stem cells in apheresis products are essential to the success of peripheral blood hematopoietic stem cell transplantation (PB-HSCT). While the flow cytometry measurement of CD34+ cells as a golden standard for stem cell count is labor and cost-intensive, hematopoietic progenitor cell number evaluated by XN Sysmex series automated hematology analyzers (XN-HPC) is suggested as a surrogate marker. MATERIALS AND METHODS: We evaluated the correlation and consistency of XN-HPC and CD34+ cell count in apheresis samples from both allogeneic donors and autologous patients during PB-HSCT...

INTRODUCTION: Carbapenem-resistant Enterobacteriaceae (CRE) infections are associated with poor outcomes, particularly among hematology-oncology patients. Appropriate use (selection and de-escalation) of antibiotics is a key component of management of febrile neutropenia particularly in high CRE prevalence regions like India. METHODS: This was a retrospective study done (April 2019-December 2021) in a dedicated oncology center in North India, which assessed the case records of the patients undergoing therapy for hematological malignancies who were diagnosed with CRE bacteremia...

BACKGROUND: Despite major treatment advances, multiple myeloma remains incurable. The outcome of patients who are refractory to immunomodulatory agents, proteasome inhibitors, and anti-CD38 monoclonal antibodies is poor, and improved treatment strategies for this difficult-to-treat patient population are an unmet medical need. METHODS: This retrospective, unicentric analysis included 38 patients with relapsed/refractory multiple myeloma or plasma cell leukemia who underwent allogeneic stem cell transplantation (allo-HSCT) between 2013 and 2022...

Allogeneic stem cell transplant remains an option for patients with myeloma. Given the unfortunate inevitability of the majority of patients, relapsing salvage therapy options are needed. Although there is a potential concern for subsequent T-cell redirection therapy in these patients, Hammons et al. provide a retrospective look at patients treated this way with no new significant adverse safety or efficacy signal. Commentary on: Hammons et al. Chimeric antigen receptor and bispecific T-cell engager therapies in multiple myeloma patients with prior allogeneic transplantation...

Various complications can influence hematopoietic cell transplantation (HCT) outcomes. Renal complications can occur during the early to late phases of HCT along with various factors. However, studies focusing on fatal renal complications (FRCs) are scarce. Herein, we analyzed 36,596 first allogeneic HCT recipients retrospectively. Overall, 782 patients died of FRCs at a median of 108 (range, 0-3,440) days after HCT. The cumulative incidence of FRCs was 1.7% and 2.2% at one and five years, respectively. FRCs were associated with older age, male sex, non-complete remission (non-CR), lower performance status (PS), and HCT comorbidity index (HCT-CI) associated with renal comorbidity in multivariate analysis...

Venetoclax is an approved treatment for relapsed/refractory Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN). We report a unique case of venetoclax monotherapy used for front-line induction and as a bridge to allogeneic hematopoietic stem cell transplantation (HCT). Venetoclax therapy resulted in rapid complete resolution of skin lesions, however, treatment interruption due to neutropenia led to brisk cancer recurrence. Fortunately, the patient responded to re-challenge and was able to undergo HCT. Venetoclax is active in the first-line treatment setting for BPDCN, however its effect on blood counts and durability of response should be further studied...

Hyperammonemia is a rare and often fatal complication following the conditioning therapy in autologous and allogeneic stem cell transplant recipients. It is characterized by anorexia, vomiting, lethargy and coma without any other apparent cause. The diagnosis is often delayed because symptoms can be subtle and ammonia is usually not included among the routine analyzes. Previous reports have not identified the molecular mechanisms behind hyperammonemia in stem cell transplant recipients. Urea cycle disorders (UCDs) are inborn errors of metabolism leading to hyperammonemia that usually presents in early childhood, whereas first presentation in adults is less common...

Multiple myeloma (MM) has witnessed improved patient outcomes through advancements in therapeutic approaches. Notably, allogeneic stem cell transplantation, proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies have contributed to enhanced quality of life. Recently, a promising avenue has emerged with chimeric antigen receptor (CAR) T cells targeting B-cell maturation antigen (BCMA), expressed widely on MM cells. To mitigate risks associated with allogenic T cells, we investigated the potential of BCMA CAR expression in natural killer cells (NKs), known for potent cytotoxicity and minimal side effects...

The Swiss Blood Stem Cell Transplantation and Cellular Therapy Group (SBST) leads a mandatory national registry for all hematopoietic stem cell transplants (HCT) and cellular therapies. After 25 years, information was available for 11,226 patients receiving an HCT (4031 allogeneic and 7195 autologous), including 925 pediatric patients. We compared patient characteristics and outcome by quinquennia 1997-2001, 2002-2006, 2007-2011, 2012-2016, and 2017-2021. There were numerous changes over time. Allogeneic transplant recipients became older (median age 33...

Chimeric antigen receptor T-cell (CAR-T) therapy and bispecific T-cell engagers (BsAb) have emerged as promising immunotherapeutic modalities in patients with relapsed and/or refractory multiple myeloma (RRMM). However, there is limited data on the safety and efficacy of CAR-T and BsAb therapies in MM patients with a prior history of allogeneic transplantation (allo-HCT). Thirty-three MM patients with prior allo-HCT received CAR-T (n = 24) or BsAb (n = 9) therapy. CAR-T therapy demonstrated an ORR of 92% (67% ≥ CR), and 73% were MRD negative...