Long Term Survival in Refractory Leukemia Patient Treated with Related HLA Haploidentical Stem Cell Transplantation

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4411-4411
Author(s):  
Bingyi Wu ◽  
Guo Kunyuan ◽  
Jing Wu
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Term Survival ◽  
Host Disease ◽  
Graft Versus Host ◽  
Disease Free

Abstract Objective: To assess the long term survival of patients with refractory leukemia treated by HLA haploidentical stem cell transplantation. Methods To analysis the outcomes of 48 cases patients with refractory leukemia underwent HLA haploidentical stem cell transplantations from August, 1998 to May, 2008. The median age was 16 years old (7–52 years old). Patients received stem cells from their parants, daughter, son, and sibling donors. Twelve patients received three HLA locus mismatched stem cells and twenty patients received two HLA locus mismatched donors stem cells. Sixteen patients were grafted one HLA mismatched donors stem cells. The conditioning regime consisted of fludara (25mg/m2 × 5d), busulfan (4mg/kg × 4d) and cyclophosphamide (60mg/kg × 2d). Median dose of rabbit anti-human lymphocyte globulin (5mg/kg × 5d) was added. CSA combined with short course of MTX were used for prophylaxis GVHD. A median dose of 6.0 × 108/kg(3–9 ×108/kg) mono-nucleated cells was grafted. The mean CD34+ cells number was 5.5 × 106/kg (3–6.5 × 106/kg) Results Forty-seven patients were successfully to be engraftment and one failed to be engraftment. The median time of white cells and platelet reconstitution was 14 days (11–20 days) and 18 days (14–20) respectively. Severe acute graft versus host disease occurred in seven patients, and six died. Seven patients suffered from intensive chronic graft versus host disease and four died with fungus infection. Seven patients relapsed and died. The median relapse time was 6 months (3 months to 24 months). Three patients died from severe diarrhea with CMV infection. Four patients died from intensive chronic graft versus host disease. Twenty patients are still survival and disease free with high karnofsky performance scores. The disease free survival is 45 percent as follow up 3 years (1 to 7 years). Conclusion: HLA haploidentical peripheral blood stem cell transplantation may be an effect therapy to refractory leukemia. And some refractory leukemia patients could benefit from HLA haploidentical peripheral blood stem cell transplantation.

scholarly journals Allogeneic Stem Cell Transplantation Combined with Mesenchymal Stem Cells Transfusion in Primary Myelofibrosis-a Single-Center Retrospective Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2054-2054
Author(s):  
Qingyuan Wang ◽  
Limin Liu ◽  
Huifen Zhou ◽  
Miao Miao ◽  
Depei Wu
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Graft Versus Host Disease ◽  
Primary Myelofibrosis ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host

Background: There are multiple treatment options that may provide symptom relief and improvement in survival in patients with primary myelofibrosis. However, allogeneic stem cell transplantation (ASCT) remains the only potentially curative option. The use and effectiveness of ASCT are limited by lethal complications, i.e., engraftment failure, acute and chronic graft-versus-host disease. Several clinical trials have used mesenchymal stem cells (MSCs) in ASCT to prevent hematopoietic stem cell (HSC) engraftment failure and to control graft versus host disease (GVHD). Objective :To evaluate the efficacy of MSCs transfusion in patients with primary myelofibrosis after allogeneic hematopoietic stem cell transplantation. Methods :The clinical data of 11 patients with primary myelofibrosis underwent ASCT and MSCs transfusion were retrospectively analyzed. Results:Among the 11 patients, 5 were male and 6 were female, with a median age of 34(20-48) years. Risk profile according the DIPSS-plus score was intermediate-1 risk(n=2) , intermediate-2 risk (n=2), and high risk (n=7). 7 of 11 patients were MF-3 and 4 cases were MF-2. Severe splenomegaly before transplantation were observed in 8 patients. Six patients were treated with ruxolitinib prior to ASCT. Among the 11 patients, 3 patients received HLA-identical sibling-ASCT, 2 received unrelated donor-ASCT and 6 received haploid ASCT from related donors. Median age of donor is 34 years old (range,20~48years old). All patients received myeloablative BuCy conditioning regime and GVHD prophylaxis consisted of cyclosporine A and MTX. Further GVHD prophylaxis consisted of ATG and MMF. All but 2 patients received peripheral blood stem cells (PBST)as graft source, the rest graft source were bone marrow (BM) plus PBST. The median number of transplanted NC cells was 12.27 (2.63 ~ 16.75) *10E8/Kg, and CD34+ cells was 5 (4.2 ~ 7.8) *10E6/Kg. BM-derived MSCs were transfused at +7d after stem cell transplantation. The median MSC infusion number was 6.5*10E6(6 ~ 65*10E6). All patients obtained hematopoietic reconstruction after transplantation, and chimerism analysis by short tandem repeat(STR) suggested complete chimerism. The median time to leukocyte engraftment was 12(range,11 ~ 20days) days and the median time to platelet engraftment was 18 days (range, 8-145 days). Leukocyte was continuously implanted in all patients whereas platelet was continuously implanted in 8 patients. Three patients did not experience any acute graft-versus-host disease (GVHD) .4 patients developed grade 1-2 acute GVHD and 4 developed grade 3-4 acute GVHD. Chronic GVHD was seen in 6 patients which were all limited disease. The median follow-up time was 24.3(1.7 ~ 48 months) months, and the expected 3-year overall survival rate was 61.4%. During the follow-up period, none relapse were observed.Four patients died, 2 of which died early after transplantation (2 months and 1.7 months). The causes of death were thrombotic microangiopathy and immunological cerebrovascular inflammation (this patient had congenital abnormalities of cerebrovascular development and had a long history of repeated epilepsy before transplantation). The other 2 patients died late after transplantation (12 months and 6.4 months) due to heart failure (the patient was with persistent atrial fibrillation before transplantation) and pulmonary infection. Conclusion: Our results demonstrated that MSCs transfusion combined with allogeneic hematopoietic stem cell transplantation is an effective treatment for primary myelofibrosis. Disclosures No relevant conflicts of interest to declare.

Long-Term Survival after HLA-Haploidentical Stem Cell Transplantation from Non-Inherited Maternal Antigen-Mismatched Family Donors: Impact of Chronic Graft-Versus-Host Disease.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5075-5075
Author(s):  
Tatsuo Ichinohe ◽  
Chihiro Shimazaki ◽  
Motohiro Hamaguchi ◽  
Arata Watanabe ◽  
Hiroyuki Ishida ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Myeloid Leukemia ◽  
Term Survival ◽  
Long Term Survival ◽  
Graft Versus Host

Abstract Background: We previously reported that T-cell-replete HLA-haploidentical hematopoietic stem cell transplantation (SCT) from a microchimeric noninherited maternal HLA antigen (NIMA)-mismatched related donor offers a feasible treatment option in patients with poor-risk hematologic malignancies who lack an immediately available stem cell source (Ichinohe T, et al. Blood2004;104:3821). However, long-term outcomes and late effects among patients undergoing such transplantation are largely unknown. Methods: We studied 16 patients who had survived more than 3 years after T-cell-replete HLA-haploidentical NIMA-mismatched SCT to evaluate the impact of late complications on morbidity and mortality. The patients received bone marrow (n=5) or peripheral blood stem cell (n=11) between 01/2001 and 07/2004 at 11 centers with a median age of 19 years (range, 2 to 56) as treatment for acute myeloid leukemia (n=6), acute lymphoblastic leukemia (n=3), chronic myeloid leukemia (n=4), and other B-cell neoplasms (n=3). At the time of SCT, 6 patients had a chemosensitive disease and 10 had a chemorefractory disease. Type of donor was NIMA-mismatched sibling in 9, mother in 6, and daughter in 1; all patient-donor pairs had two or three serologic mismatches at HLA-A, −B, and −DR in the graft-versus-host direction. Organ-specific symptoms related to chronic graft-versus-host disease (cGVHD) and their severity were evaluated by clinical scoring system proposed by the National Institutes of Health consensus development project. Results: At a median follow-up of 56 months (range, 38 to 74), 13 (81%) of 16 patients were alive and free of their primary disease. One patient was alive with relapsed disease; 2 died from bronchiolitis obliterans at 51 and 52 months in continuous remission. Karnofsky or Lansky performance score among 14 survivors was 100% in 6 (43%), 80–90% in 5 (36%), 70% in 2 (14%), and less than 70% in 1 (7%). Thirteen (81%) patients developed extensive cGVHD and eleven of them experienced organ symptoms corresponding to the consensus score greater than 1. The commonly involved organs (score>1) were lungs (n=5), skin (n=4), eyes (n=3), and liver (n=3). Seven patients were successfully withdrawn from immunosuppressive agents between 3 and 46 months (median, 19) after transplantation. Conclusions: T-cell-replete HLA-haploidentical SCT from a microchimeric NIMA-mismatched donor confers long-term survival in selected patients without compromising their performance status, although a high incidence of moderate to severe cGVHD may limit its usefulness as compared with conventional SCT.

scholarly journals Microbiota long-term dynamics and prediction of acute graft-versus-host disease in pediatric allogeneic stem cell transplantation

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Anna Cäcilia Ingham ◽  
Katrine Kielsen ◽  
Hanne Mordhorst ◽  
Marianne Ifversen ◽  
Frank M. Aarestrup ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Host Disease ◽  
Graft Versus Host ◽  
Three Body ◽  
Nasal Microbiota ◽  
Acute Graft

Abstract Background Patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) exhibit changes in their gut microbiota and are experiencing a range of complications, including acute graft-versus-host disease (aGvHD). It is unknown if, when, and under which conditions a re-establishment of microbial and immunological homeostasis occurs. It is also unclear whether microbiota long-term dynamics occur at other body sites than the gut such as the mouth or nose. Moreover, it is not known whether the patients’ microbiota prior to HSCT holds clues to whether the patient would suffer from severe complications subsequent to HSCT. Here, we take a holobiont perspective and performed an integrated host-microbiota analysis of the gut, oral, and nasal microbiota in 29 children undergoing allo-HSCT. Results The bacterial diversity decreased in the gut, nose, and mouth during the first month and reconstituted again 1–3 months after allo-HSCT. The microbial community composition traversed three phases over 1 year. Distinct taxa discriminated the microbiota temporally at all three body sides, including Enterococcus spp., Lactobacillus spp., and Blautia spp. in the gut. Of note, certain microbial taxa appeared already changed in the patients prior to allo-HSCT as compared with healthy children. Acute GvHD occurring after allo-HSCT could be predicted from the microbiota composition at all three body sites prior to HSCT. The reconstitution of CD4+ T cells, TH17, and B cells was associated with distinct taxa of the gut, oral, and nasal microbiota. Conclusions This study reveals for the first time bacteria in the mouth and nose that may predict aGvHD. Monitoring of the microbiota at different body sites in HSCT patients and particularly through involvement of samples prior to transplantation may be of prognostic value and could assist in guiding personalized treatment strategies. The identification of distinct bacteria that have a potential to predict post-transplant aGvHD might provide opportunities for an improved preventive clinical management, including a modulation of microbiomes. The host-microbiota associations shared between several body sites might also support an implementation of more feasible oral and nasal swab sampling-based analyses. Altogether, the findings suggest that the microbiota and host factors together could provide actionable information to guiding precision medicine.

scholarly journals Microbiota long-term dynamics and prediction of acute graft-versus-host-disease in pediatric allogeneic stem cell transplantation

2021 ◽  
Author(s):  
Anna Cäcilia Ingham ◽  
Katrine Kielsen ◽  
Hanne Mordhorst ◽  
Marianne Ifversen ◽  
Frank M. Aarestrup ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Healthy Children ◽  
Host Disease ◽  
Graft Versus Host ◽  
Three Body ◽  
Acute Graft

AbstractBackgroundPatients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) exhibit changes in their gut microbiota and are experiencing a range of complications, including acute graft-versus-host disease (aGvHD). It is unknown if, when, and under which conditions a re-establishment of microbial and immunological homeostasis occurs. It is also unclear whether microbiota long-term dynamics occur at other body sites than the gut such as the mouth or nose. Moreover, it is not known whether the patients’ microbiota prior to HSCT holds clues to whether the patient would suffer from severe complications subsequent to HSCT. Here, we performed integrated host-microbiota analyses of the gut, oral, and nasal microbiotas in 29 children undergoing allo-HSCT.ResultsThe bacterial diversity decreased in the gut, nose, and mouth during the first month and reconstituted again 1-3 months after allo-HSCT. The microbial community composition traversed three phases over one year. Distinct taxa discriminated the microbiota temporally at all three body sides, including Enterococcus spp., Lactobacillus spp., and Blautia spp. in the gut. Of note, certain microbial taxa appeared already changed in the patients prior to allo-HSCT as compared to healthy children. Acute GvHD occurring after allo-HSCT could be predicted from the microbiota composition at all three body sites prior to HSCT, in particular from Parabacteroides distasonis, Lachnospiraceae NK4A136 sp. and Lactobacillus sp. abundances in the gut. The reconstitution of CD4+ T cells, TH17 and B cells was associated with distinct taxa of the gut, oral, and nasal microbiota.ConclusionsThis study reveals for the first time bacteria in the mouth and nose that may predict aGvHD. Surveillance of the microbiota at different body sites in HSCT may be of prognostic value and could assist in guiding personalized treatment strategies. The identification of distinct bacteria that have a potential to predict post-transplant aGvHD might provide opportunities for an improved preventive clinical management, including a modulation of microbiomes. The host-microbiota associations shared between several body sites might also support an implementation of more feasible oral and nasal swab sampling-based analyses. Altogether, the findings suggest that both, host factors and the microbiota, could provide actionable information to guiding precision medicine.

scholarly journals Microbiota long-term dynamics and prediction of acute graft-versus-host-disease in pediatric allogeneic stem cell transplantation

2021 ◽  
Author(s):  
Anna Cäcilia Ingham ◽  
Katrine Kielsen ◽  
Hanne Mordhorst ◽  
Marianne Ifversen ◽  
Frank M Aarestrup ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Healthy Children ◽  
Host Disease ◽  
Graft Versus Host ◽  
Three Body ◽  
Acute Graft

Abstract Background Patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) exhibit changes in their gut microbiota and are experiencing a range of complications, including acute graft-versus-host disease (aGvHD). It is unknown if, when, and under which conditions a re-establishment of microbial and immunological homeostasis occurs. It is also unclear whether microbiota long-term dynamics occur at other body sites than the gut such as the mouth or nose. Moreover, it is not known whether the patients’ microbiota prior to HSCT holds clues to whether the patient would suffer from severe complications subsequent to HSCT. Here, we take a holobiont perspective and performed an integrated host-microbiota analysis of the gut, oral, and nasal microbiotas in 29 children undergoing allo-HSCT.Results The bacterial diversity decreased in the gut, nose, and mouth during the first month and reconstituted again 1-3 months after allo-HSCT. The microbial community composition traversed three phases over one year. Distinct taxa discriminated the microbiota temporally at all three body sides, including Enterococcus spp., Lactobacillus spp., and Blautia spp. in the gut. Of note, certain microbial taxa appeared already changed in the patients prior to allo-HSCT as compared to healthy children. Acute GvHD occurring after allo-HSCT could be predicted from the microbiota composition at all three body sites prior to HSCT. The reconstitution of CD4+ T cells, T H 17 and B cells was associated with distinct taxa of the gut, oral, and nasal microbiota. Conclusions This study reveals for the first time bacteria in the mouth and nose that may predict aGvHD. Monitoring of the microbiota at different body sites in HSCT patients, and particularly through involvement of samples prior to transplantation, may be of prognostic value and could assist in guiding personalized treatment strategies. The identification of distinct bacteria that have a potential to predict post-transplant aGvHD might provide opportunities for an improved preventive clinical management, including a modulation of microbiomes. The host-microbiota associations shared between several body sites might also support an implementation of more feasible oral and nasal swab sampling-based analyses. Altogether, the findings suggest that the microbiota and host factors together could provide actionable information to guiding precision medicine.

Donor-derived CMV-specific T cells reduce the requirement for CMV-directed pharmacotherapy after allogeneic stem cell transplantation

Blood ◽  
2013 ◽  
Vol 121 (18) ◽  
pp. 3745-3758 ◽  
Author(s):  
Emily Blyth ◽  
Leighton Clancy ◽  
Renee Simms ◽  
Chun K. K. Ma ◽  
Jane Burgess ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Allogeneic Stem Cell Transplantation ◽  
Organ Damage ◽  
Host Disease ◽  
Graft Versus Host ◽  
Key Points

Key Points Infusion of CMV-specific T cells early posttransplant does not increase acute or chronic graft-versus-host disease. CMV-specific T cells early posttransplant reduce the need for pharmacotherapy without increased rates of CMV-related organ damage.

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