scholarly journals Erratum to “Increased Type 1 Immune Response in the Bone Marrow Immune Microenvironment of Patients with Poor Graft Function after Allogeneic Hematopoietic Stem Cell Transplantation” [Biol Blood Marrow Transplant 2016;22:1376-1382]

2016 ◽  
Vol 22 (12) ◽  
pp. 2285
Author(s):  
Yu-Tong Wang ◽  
Yuan Kong ◽  
Yang Song ◽  
Wei Han ◽  
Yuan-Yuan Zhang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Immune Response ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Graft Function ◽  
Marrow Transplant ◽  
Immune Microenvironment ◽  
Hematopoietic Stem ◽  
Poor Graft Function

scholarly journals Impaired Hematopoiesis after Allogeneic Hematopoietic Stem Cell Transplantation: Its Pathogenesis and Potential Treatments

Hemato ◽  
2021 ◽  
Vol 2 (1) ◽  
pp. 43-63
Author(s):  
Masahiro Imamura
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Hematopoietic Stem Cells ◽  
Graft Failure ◽  
Graft Function ◽  
Hematopoietic Stem ◽  
Poor Graft Function ◽  
Bone Marrow Niches

Impaired hematopoiesis is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Bone marrow aplasia and peripheral cytopenias arise from primary and secondary graft failure or primary and secondary poor graft function. Chimerism analysis is useful to discriminate these conditions. By determining the pathogenesis of impaired hematopoiesis, a timely and appropriate treatment can be performed. Hematopoietic system principally consists of hematopoietic stem cells and bone marrow microenvironment termed niches. Abnormality in hematopoietic stem and progenitor cells and/or abnormality in the relevant niches give rise to hematological diseases. Allo-HSCT is intended to cure each hematological disease, replacing abnormal hematopoietic stem cells and bone marrow niches with hematopoietic stem cells and bone marrow niches derived from normal donors. Therefore, treatment for graft failure and poor graft function after allo-HSCT is required to proceed based on determining the pathogenesis of impaired hematopoiesis. Recent progress in this area suggests promising treatment manipulations for graft failure and poor graft function.

Poor Graft Function in Recipients of T Cell Depleted (TCD) Allogeneic Hematopoietic Stem Cell Transplants (HSCT) Is Mostly Related to Viral Infections and Anti-Viral Therapy.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3147-3147 ◽  
Author(s):  
Roni Tamari ◽  
Sheetal Ramnath ◽  
Deborah Kuk ◽  
Craig S. Sauter ◽  
Doris M Ponce ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
T Cells ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Viral Infections ◽  
Graft Function ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Poor Graft Function

Abstract Abstract 3147 Introduction: Poor graft function (PGF) without immune rejection, defined as persistent cytopenias with hypocellular marrow and full donor myeloid chimerism, can be a life-threatening complication after allogeneic HSCT. It is commonly caused by viral infectious, myelosuppressive drugs like antivirals, and graft-vs-host disease (GvHD). Treatment options include supportive therapy with transfusions and growth factors and in severe cases administration of additional hematopoietic stem cells (HSCs) from the same donor without conditioning (stem cell boost). The incidence, natural history, and the indications for stem cell boost therapy are not well defined. Aims: To assess the incidence, etiologies, and indications for stem cell boost for PGF in a homogeneous group of patients with advanced MDS and AML who underwent TCD HSCT from matched or mismatched related or unrelated donors after conditioning with the same myeloablative regimen. Patients and methods: Poor graft function was defined as persistent neutropenia (ANC <1,000 μL and G-CSF administration x3 in 30 days), thrombocytopenia (platelets <50,000 μL or platelets transfusion × 4 in 30 days), and/or hemoglobin <8 g//dL after engraftment with hypocellular BM and full donor myeloid chimerism. Severe PGF was defined as ANC <500 μL, red cell transfusion-dependent anemia with reticulocytopenia of < 20,000 μL, and platelets <20,000 μL. The patient population in which this study was done included 42 patients enrolled between 09/2009 and 05/2012 in a phase 2 trial of palifermin peri-transplant to reduce transplant-related mortality. The median age was 57.5 years (1–65). All patients received the same myeloablative conditioning regimen with busulfan, melphalan, fludarabine, rabbit ATG and palifermin peri-transplant. G-CSF mobilized donor peripheral blood stem cells underwent CD34+ selection and depletion of T cells using CliniMACS immunomagnetic selection columns (Milteny Biotec). Donors were HLA matched (31; 13 related and 18 unrelated) or mismatched unrelated (11). Chimerism was determined in bone marrow as well as neutrophils, B cells, and T cells by short tandem repeat analysis on DNA extracted from bone marrow and peripheral blood cell subsets. Results: Forty-one patients were evaluable for this analysis; 1 patient was not included as he rejected the allograft shortly after engraftment. There were 8 cases of PGF with a cumulative incidence (CI) at 1 year of 18% (13% HLA matched, 33% HLA mismatch). The etiology was infection in 7 cases, and unknown in the 8th case. This patient presented with presumed autoimmune anemia and thrombocytopenia associated with a hypercellular marrow and did not respond to multiple lines of therapies. Her marrow became later hypocellular and met the criteria for PGF. None of the PGF cases in this series was associated with GvHD at the time of diagnosis of PGF. The infectious etiologies included: 6 viral infections and 1bacterial sepsis + myelosuppressive drugs. The most common viral etiology associated with PGF was CMV (50%). The 1-year CI of PGF in CMV seropositive patients was 25% and in CMV seronegative patients was 14%. Of note, HHV6 viremia was detected in patients with PGF. HHV6 is not routinely monitored, however, making it difficult to establish a causative role. All patients had moderate PGF at diagnosis and 3 cases had worsening of cytopenias and met the criteria for severe PGF. To date, 3 PGF patients have died from EBV-PTLD, adenovirus infection or GVHD (developed after CMV treatment with liposomal cidofovir), 3 continue to suffer from PGF and 2 patients are alive with recovered good blood counts after eradication of CMV. Of the 3 patients with persistent PGF, one received a TCD boost with no response, and 2 continued to be treated for CMV viremia. A stem cell boost was indicated if pancytopenia persisted despite eradication of cause of the PGF. In this small series, there were not enough events to evaluate association between PGF and CD34 cell dose, CD3 cell dose or day 100 T-cell chimerism. Conclusions: In this homogenous population of patients with MDS who underwent TCD allogeneic HSCT, the incidence of PGF is about 20%. The most common cause was viral infection with predominance of CMV. Therefore, strategies to prevent CMV reactivation in patients undergoing allogeneic HSCT has the potential to reduce the risk of PGF and avoid the need for infusion of additional stem cells. Disclosures: No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document