scholarly journals Treosulfan-based conditioning for hematopoietic stem cell transplantation in patients with Diamond–Blackfan anemia

2021 ◽  
Vol 20 (2) ◽  
pp. 40-45
Author(s):  
S. A. Radygina ◽  
S. N. Kozlovskaya ◽  
A. P. Vasilieva ◽  
I. P. Shipitsina ◽  
А. А. Bogoyavlenskaya ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Medical Research ◽  
Cell Transplantation ◽  
Acute Gvhd ◽  
Hematopoietic Stem ◽  
Pediatric Hematology ◽  
Diamond Blackfan Anemia ◽  
National Medical

Busulfan-based conditioning regimens before hematopoietic stem cell transplantation (HSCT) in patients with Diamond–Blackfan anemia (DBA) are the standard therapy for a long time. Unfortunately, the high incidence of toxic complications is the cause of transplant-related mortality (TRM) or low quality of life. Treosulfan-based conditioning is very attractive, however only limited data exists of its administration in DBA patients. In this article, we present the experience of treosulfan usage along with novel approaches to “graft versus host” disease (GVHD) prophylaxis in Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. The study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. From 2012 to 2020, 9 patients with DBA underwent HSCT. Matched unrelated donors were used in 7 patients, mismatched related in 1, and HLA-identical sibling in 1 patient. All patients received treosulfan-based conditioning. The sources of HSC were bone marrow (n = 3) and peripheral blood after TCRab+/CD19+ graft depletion (n = 6). Eight patients received various regimens of post-transplant prophylaxis, included calcineurin inhibitors alone or in combinations, 1 patient – mycophenolate mofetil. All transplanted patients engrafted. Median follow-up in survivors (n = 8) was 35.6 months. One patient (Karnofsky-index before HSCT 40%) died on day +58 due to multio rgan failure, caused by toxic and infectious complications. Besides, three patients had clinically signifiant toxic complications: oral mucositis grade 3 in 1 patient, treosulfan skin toxicity in 2, and moderate veno-occlusive-disease in 1 patient. Five patients had acute GVHD grade II with complete response to the 1st line therapy. There was no evidence of acute GVHD grade III–IV as well as chronic GVHD. Our data demonstrate, that treosulfan-based conditioning, alongside new cellular engineering approaches is effctive options for HSCT outcomes in patients with DBA.

scholarly journals Hematopoietic stem cell transplantation with TCRαβ+/CD19+ - graft depletion for hemophagocytic lymphohistiocytosis

2020 ◽  
Vol 19 (2) ◽  
pp. 38-45
Author(s):  
A. K. Kantulaeva ◽  
E. I. Gutovskaya ◽  
A. L. Laberko ◽  
S. A. Radygina ◽  
S. N. Kozlovskaya ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Medical Research ◽  
Cell Transplantation ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Hematopoietic Stem ◽  
Pediatric Hematology ◽  
National Medical ◽  
Conditioning Regimens

The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology. We present the outcomes of allogeneic hematopoietic stem cell transplantation (HSCT) with TCRab+/CD19+ graft depletion in patients with genetic hemophagocytic lymphohistiocytosis (HLH) at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology from 2012 to 2019. Thirty-six patients with various HLH: familial HLH (n = 20), X-linked lymphoproliferative disease (XLP) type 1 (n = 4), XLP type 2 (n = 9), Griscelli syndrome (n = 1), Chediak–Higashi syndrome (n = 2) received HSCT. Conditioning regimens were based on treosulfan in 9 patients, or on two alkylating agents: treosulfan with either melphalan, or thiotepa in 27 patients; all 36 patients received fludarabine and serotherapy. Thirty-two patients received rituximab 100 mg/m2 the day before stem cell infusion. Post- HSCT “graft versus host” disease (GvHD) prophylaxis was used in 29 patients. As a graft source peripheral blood stem cells from matched unrelated (n = 23), matched related (n = 3) and haploidentical family (n = 10) donors after TCRαβ+/CD19+ graft depletion were used. The cumulative incidence of primary and secondary graft failure in all patients was 0.11 (95% CI 0.04–0.29). The incidence of acute GvHD was limited to stage I-II. Overall survival was 0.91 (95% CI 0.82–1) without any significant differences in various donor groups (p = 0.33) as well as different conditioning regimens (p = 0.75). Allogeneic HSCT with TCRαβ+/CD19+ graft depletion after treosulfan-based conditioning is effective and safe technology for patients with genetic HLH.

Impact of High-Resolution HLA Matching on Outcomes of Unrelated Donor Hematopoietic Stem Cell Transplantation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5446-5446
Author(s):  
Seok Yun Kang ◽  
Hyeoung Il Kim ◽  
Hyun Woo Lee ◽  
Jun Ho Jang ◽  
Joon Seong Park ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Resolution ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Survival Data ◽  
Myeloid Leukemia ◽  
Acute Gvhd ◽  
Hla Matching ◽  
Hematopoietic Stem

Abstract Objective: We assessed the impact of high-resolution genotypic results of human leukocyte antigen (HLA) for all major class I and II loci between donors and recipients in the outcome of unrelated hematopoietic stem cell transplantation (HSCT). Method: Between 1999 and 2005, high-resolution genotyping for HLA-A, -B, -C and -DRB1 was performed for 23 unrelated HSCT. All the patients were typed as HLA identical by serologic technique and then they were also typed HLA identical by high resolution technique. Unrelated bone marrow transplantation using DNA-based high resolution HLA compatibilities were considered in the analyses of clinical outcomes such as hematopoietic engraftment, acute GVHD, and survival. And then, we compared with patients who received related HSCT (same institute, same duration) and also unrelated HSCT data from IBMTR. Results: Median follow up duration was 9 months (1–51). Fifteen patients were male and 8 were female. Median age was 22 years (range 6–52). Median time from diagnosis to transplantation was 7 months (range 4–63). Eight patients of acute myeloid leukemia (AML), 6 of chronic myeloid leukemia (CML, 2 of 6 were in blast crisis), 4 of acute lymphoid leukemia (ALL), 3 of severe aplastic anemia and each case of juvenile myelomonocytic leukemia and myelodysplastic syndrome were enrolled. Median value of total nucleated cell and CD34 positive cell count was 3.51 (1.06–20.7) x 108/kg and 4.88 (1.33–46.9) x 106/kg, respectively. The conditioning regimen and prophylaxis for graft versus host disease (GVHD) were not different from conventional HSCT except one case of non-myeloablative transplantation. Median value of granulocytic (absolute granulocyte count > 500/mm3) and platelet (> 20,000/mm3) engraftment were D + 16, D + 17, respectively. Grade II acute GVHD developed in 4 patients (2 patients subsequently proceded to chronic GVHD). Treatment related mortality was 2 out of 23 patients (8.7%). Median value of overall survival duration was 30 months. For AML patients, 3-year survival rate was 72.9 %. Conclusions: Our survival data for unrelated HSCT based on high resolution genotyped HLA matching was superior to unrelated HSCT. Although the sample size is small, the survival data of AML patients (CR1 at transplant) was superior to the survivals of related HSCT, as well as that of unrelated HSCT. The findings were that transplantation using unrelated donors selected by high-resolution genotype identity improves the transplantation outcomes similar degree to the result of the related HSCT.

Large Granular Lymphocyte Expansion Following Allogeneic Hematopoietic Stem Cell Transplantation Is Associated with the Presence of CMV Reactivation and Probably with Acute GvHD and Shows An Indolent Outcome.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3461-3461
Author(s):  
Sabine Nann ◽  
Alexander Tzankov ◽  
Nathan Cantoni ◽  
Jörg Halter ◽  
Dominik Heim ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Gene Rearrangement ◽  
Acute Gvhd ◽  
Clinical Signs ◽  
Hematopoietic Stem ◽  
Cmv Reactivation ◽  
Lgl Leukemia

Abstract Abstract 3461 Expansion of CD3+ large granular lymphocytes (T-LGL) can be observed in situations such as viral infection, autoimmune disease, malignant neoplasm, and following allogeneic hematopoietic stem cell transplantation (HSCT). We sought to evaluate in patients treated with allogeneic HSCT incidence, characteristics, and clinical significance of persistent post-transplant T-LGL expansion. In this single center retrospective cohort study, we included all patients seen between January/08 and December/09 in our out-patient clinic for their regular follow-up. In patients with persistent lymphocytosis (>3 G/l for >3months) and an abnormal CD4/CD8 ratio, an extensive immunophenotyping was assessed; in case of an abnormal expansion of T-LGL cells a TCR gene rearrangement was performed. In 14 (7%) out of 215 evaluated patients a T-LGL expansion was diagnosed. Patients' characteristics with and without T-LGL expansion are summarized in Table 1. The median time between HSCT and diagnosis of lymphocytosis was 12 months (1-58). The median lymphocyte count was 4.24 G/l (3.0-26.5). The median duration of lymphocytosis was 29 (4-176) months. In 13/14 cases there was a CD3+/CD8+ immunophenotype, in 1 case was CD3+CD4+. In 5/14 patients a clonal TCR-gene rearrangement was observed. None of the patients presented neutropenia. Mild anemia was observed in 8/14 patients (57%), and thrombocytopenia in 2/14 patients; both changes were most probably not related with the T-LGL expansion. None of the patients had typical clinical signs of a T-LGL leukemia. In the univariate analysis acute GvHD and CMV reactivation were the only variables associated with T-LGL expansion, In the multivariate the relative risk (RR) of CMV reactivation was 5.063 (95%CI: 1.586–16.160; p=0.006) and the RR of acute GvHD grade 2–4 was 2.831 (95%CI: 0.831–9.648; p=0.096). Conclusion: we detected a T-LGL expansion in 7% of patients after HSCT. No symptoms or clinical signs related to T-LGL leukemia were observed. The T-LGL expansions, even when monoclonal, showed a chronic but indolent course. They have to be considered rather as an expression a chronic stimulation, triggered by causes such CMV reactivation or acute GvHD rather than as a malignant transformation. The question whether a T-LGL expansion plays a GvL role could not be answered in this study due to the small number of patients and the study design. Disclosures: No relevant conflicts of interest to declare.

Long Term Follow-up of Haploidentical Hematopoietic Stem Cell Transplantation without in Vitro T Cell Depletion for the Treatment of Hematological Malignancies: 9-Year Experience of a Single Center

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 839-839 ◽  
Author(s):  
Xiao Jun Huang
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Acute Gvhd ◽  
Disease Stage ◽  
Hematopoietic Stem

Abstract 839FN2 Many patients who require allogeneic hematopoietic stem cell transplantation (allo-HSCT) lack a human leukocyte antigen (HLA)-matched donor. Recently, we developed a new strategy named GIAC protocol for HLA-mismatched/haploidentical transplantation from family donors that combines granulocyte-colony stimulating factor (G-CSF) primed bone marrow (G-BM) and peripheral blood stem cells (PBSC) without in vitro T-cell depletion (TCD). For the past nine years, promising results for HLA-mismatched allo-HSCT without in vitro TCD have been achieved at our institute using this protocol. From May 2002 to December 2010, 820 patients, including 206 in high-risk group, underwent transplantation from haploidentical family donors. Eight-hundred and eleven patients (99%) achieved sustained, full donor chimerism. The incidence of grade 2–4 acute graft-versus-host disease (GVHD) was 42.9%, and that of grades 3 and 4 was 14.0% which was not associated with the extent of HLA disparity.Figure 1Cumulative incidence of acute GVHD grade 2–4 according to HLA disparity.Figure 1. Cumulative incidence of acute GVHD grade 2–4 according to HLA disparity.Figure 2Probability of LFS after haploidentical HSCT according to disease stage (p =.001).Figure 2. Probability of LFS after haploidentical HSCT according to disease stage (p =.001). Disclosures: No relevant conflicts of interest to declare.

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