Pulmonary Complications after T-Cell Depleted Allogeneic Stem Cell Transplantation: Low Incidence and Strong Association with Acute GVHD.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1821-1821
Author(s):  
Cynthia Huisman ◽  
Hanneke M. van der Straaten ◽  
Marijke R. Canninga-van Dijk ◽  
Rob Fijnheer ◽  
Leo F. Verdonck
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Pulmonary Complications ◽  
Hematopoietic Stem ◽  
Control Subjects ◽  
Significant Difference

Abstract Lung injury limits the success of hematopoietic stem cell transplantation (HSCT). The overall incidence varies from 30–50% and noninfectious causes occur in one third to one half of these. We reviewed pulmonary complications in 369 patients who received either allo-BMT or allo-PBSCT at our institution between 1993 and 2003. Control subjects were selected from the same database and matched on sex, underlying diagnosis, age, type of transplantation and cytomegalovirus-serostatus. For all patients the conditioning myeloablative regimen consisted of cyclophosphamide (60 mg/kg/day for 2 days) followed by total body irradiation (total lung dose 850 cGy). The graft was partially T-cell depleted (1–2 x 105 T cells/kg). Sixty-one patients (16.5%) developed pulmonary complications, which were diagnosed at a median of 22 weeks after transplantation (range 2–263). Twenty-one patients (5.7%) developed infectious pneumonia. Non-infectious complications were further subclassified as BO (3.5%), BOOP (0.5%), DAH (0.8%), IPS (5.4%) or mixed etiology (0.5%). Acute GVHD ≥ grade II was significantly more common in patients with pulmonary complications than in the controls (36/61 versus 24/61 patients, P=0.02). There was no significant difference in the incidence of chronic GVHD (in 26/48 pulmonary patients versus 20/55 controls, P=0.1). Median survival was 41 weeks (range 4–583) for the pulmonary patients and 173 weeks (range 8–582) for the control subjects. These data illustrate that the incidence of pulmonary complications is low after T-cell depleted HSCT and demonstrate a clear association with acute GVHD. Improvement of the poor outcome of pulmonary complications is of utmost importance. Current studies at our institution are focused at the detection of early markers so that possible pre-emptive-like therapy can be initiated before symptomatic lung damage arises.

The Effect of Costimulatory Moleculars on Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4875-4875
Author(s):  
Zhenhua Qiao ◽  
Fang Ye ◽  
Lei Zu
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Group A ◽  
Group B

Abstract Objective: To explore the effect of costimulatory molecular and CD25 expressed on peripheral CD4+ T lymphocytes on graft-versus-host disease(GVHD) after allogeneic hematopoietic stem cell transplantation(allo-HSCT). Methods: 1. The 21 patients who suffered of hematology diseases or malignant solid tumors and were underwent allo-HSCT and 10 normal individuals were enrolled in the study.2. For the sake of difference conditioning regimens we divided the 21 patients into two groups: patients undergoing non-myeloablative stem cell transplantation(NST) belonged to group A, others undergoing traditional myeloablative stem cell transplantation belonged to group B; we divided them into five groups for with GVHD or without GVHD and types of GVHD: group 1(group A with acute GVHD), group 2(group A with chronic GVHD), group 3(group B with acute GVHD), group 4(group B without GVHD), group 5(group A without GVHD).3. The levels of CD28, CD80, CD152 and CD25 expressions on peripheral CD4+ T lymphocytes were detected by three colors flow cytometry (FCM)in different time(before allo-HSCT,7days,14days,21days,30days after allo-HSCT, the time of GVHD and the time after GVHD treated).4.STR-PCR for detecting micro-satellites chimeras forming. Results: 1. All 21 patients achieved engraftment. By STR-PCR assay,12 cases formed complete chimeras(CC) and 9 cases formed mixed chimeras(MC). In group A,3 cases developed acute GVHD and 4 cases developed chronic GVHD; in group B,4 cases developed aGVHD. The incidence of GVHD and infection rates between group A and B has no difference(X2=3.711, P=0.144).2. Among these 21 cases,5 cases died:2 cases died of multiple organs function failure due to primary disease relapse,1 case died of bleeding in brain and 2 cases died of liver function failure for the sake of complicated with acute GVHD; others survive with disease free till present.3. The results of multivariate logistic regression models and Kaplan-Meier survival curves analyses showed: age, sex, infection, HLA-type, blood type, conditioning regiment and the times of absolute neutrophil counts and platelets recovering to normal, had no association with the incidence of GVHD;A multivariate COX survival function model analysis showed CD4CD152 and CD4CD25 are independent prognostic factors for GVHD(X2=13.128, P<0.0001).4. Patients with GVHD demonstrated higher CD4+CD28+ and CD4+CD80+ T cell levels than those without GVHD(P<0.01);patients with aGVHD demonstrated higher than those with cGVHD(P<0.05) and without GVHD(P<0.05); Patients with GVHD demonstrated lower CD4+CD152+ and CD4+CD25+ T cell levels than those without GVHD(P<0.01); the same result occurs between aGVHD and cGVHD and without GVHD. After effective treatment, unnormal CD4+CD28+, CD4+CD80+, CD4+CD152+ and CD4+CD25+ T cell levels recovered to the levels before transplantation. Conclusions: The incidences of GVHD between NST and traditional myeloablative stem cell transplantation had no difference. B7-CD28/CD152 costimulatory pathway plays a critical role in developing of GVHD. Peripheral CD4+CD28+, CD4+CD80+, CD4+CD152+ and CD4+CD25+ T cell levels were relative to recipient GVHD, especially CD4+CD152+ and CD4+CD25+ T cell levels. Down-grade CD4+CD28+ and CD4+CD80+ T cell levels and up-grade CD4+CD152+ and CD4+CD25+T cell levels could reduce the incidence of GVHD.

Outcome of Non-T-Cell-Depleted Hematopoietic Stem Cell Transplantation between HLA-Haploidentical Non-Inherited Maternal Antigen (NIMA)-Mismatched Family Members in Childhood.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2913-2913
Author(s):  
Takao Yoshihara ◽  
Keiko Okada ◽  
Hiromasa Yabe ◽  
Michihiro Kobayashi ◽  
Atsushi Kikuta ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Family Members ◽  
Hematopoietic Stem

Abstract Sporadic cases of successful non-T-cell-depleted (TCD) hematopoietic stem cell transplantation (SCT) from HLA-haploidentical family members mismatched for noninherited maternal antigens (NIMAs) have been reported over the last few years. This kind of SCT is based on the hypothesis that long-term feto-maternal microchimerism is associated with acquired immunologic hyporesponsiveness to NIMA or inherited paternal antigens (IPAs). To confirm the effectiveness and safety of NIMA-mismatched SCT in a large cohort, we retrospectively surveyed the outcomes of 76 children (44 boys, 32 girls; median age 7 years, range, 0–18) with either advanced non-malignant disorders (n=10), hematological malignancies (n=62) or solid tumors (n=4) who underwent T-cell-replete HLA-2-loci- or HLA-3-loci incompatible SCT from NIMA-mismatched donors (mother, n=53; NIMA-mismatched sibling, n=12) or other family donors (father/NIPA-mismatched sibling) (n=11) between 01/2000 and 12/2004. Disease status of malignant disease at SCT was as follows: CR1/CR2/CP in 19 and chemorefractory in 47. Types of grafts were bone marrow in 40 and peripheral blood stem cells in 35. Feto-maternal michrochimerism was detected in 32 out of 35 mothers tested and 8 out of 8 NIMA-mismatched sibling donors. GVHD prophylaxis consisted of tacrolimus-based regimen in 73. All but two patients achieved sustained neutrophil engraftment at median of 16.5 days (range, 10–29). Grade II to IV acute GVHD occurred in 36 of 73 evaluable patients (49%) between days 7 and 36 (median, 17). In non-malignant disorders, no severe (grade III/IV) acute GVHD was observed, while in malignant disorders, severe acute GVHD occurred in 21 (32%) of 65 evaluable patients. Twenty-two out of 41 evaluable patients (54%) who survived more than 6 months had extensive chronic GVHD. As of 04/2005, in non-malignant disorders, all 9 patients who obtained engraftment were alive. In malignant disorders, twenty-nine out of 66 patients (44%) were alive and 25 of them were disease-free with median follow-up of 25 (range, 4 to 57) months. Death were due to disease progression (n=22), infection (n=6), GVHD (n=4) and others (n=4). These results suggest that pediatric patients who lack immediate access to a conventional stem cell source can obtain successful results with non-TCD transplants from an HLA-haploidentical NIMA-mismatched donor.

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.

scholarly journals HLA-haploidentical TCRαβ+/CD19+-depleted stem cell transplantation in children and young adults with Fanconi anemia

2021 ◽  
Vol 5 (5) ◽  
pp. 1333-1339
Author(s):  
Luisa Strocchio ◽  
Daria Pagliara ◽  
Mattia Algeri ◽  
Giuseppina Li Pira ◽  
Francesca Rossi ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Fanconi Anemia ◽  
Chronic Gvhd ◽  
Prospective Trial ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Platelet Recovery

Abstract We report on the outcome of 24 patients with Fanconi anemia (FA) lacking an HLA matched related or unrelated donor, given an HLA-haploidentical T-cell receptor αβ (TCRαβ+) and CD19+ cell-depleted hematopoietic stem cell transplantation (HSCT) in the context of a prospective, single-center phase 2 trial. Sustained primary engraftment was achieved in 22 (91.6%) of 24 patients, with median time to neutrophil recovery of 12 days (range, 9-15 days) and platelet recovery of 10 days (range, 7-14 days). Cumulative incidences of grade 1 to 2 acute graft-versus-host disease (GVHD) and chronic GVHD were 17.4% (95% confidence interval [CI], 5.5%-35.5%) and 5.5% (95% CI, 0.8%-33.4%), respectively. The conditioning regimen, which included fludarabine, low-dose cyclophosphamide and, in most patients, single-dose irradiation was well tolerated; no fatal transplant-related toxicity was observed. With a median follow-up of 5.2 years (range, 0.3-8.7 years), the overall and event-free survival probabilities were 100% and 86.3% (95% CI, 62.8%-95.4%), respectively (2 graft failures and 1 case of poor graft function were considered as events). The 2 patients who experienced primary graft failure underwent a subsequent successful HSCT from the other parent. This is the first report of FA patients given TCRαβ+/CD19+-depleted haplo-HSCT in the context of a prospective trial, and the largest series of T-cell–depleted haplo-HSCT in FA reported to date. This trial was registered at www.clinicaltrials.gov as #NCT01810120.

scholarly journals The Addition of Sirolimus to GVHD Prophylaxis After Allogeneic Hematopoietic Stem Cell Transplantation: A Meta-Analysis of Efficacy and Safety

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaoli Chen ◽  
Hengrui Sun ◽  
Kaniel Cassady ◽  
Shijie Yang ◽  
Ting Chen ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Acute Gvhd ◽  
Meta Analysis ◽  
Chronic Gvhd ◽  
Hematopoietic Stem ◽  
Safety And Efficacy

ObjectiveThe objective of this study was to evaluate the safety and efficacy of sirolimus (SRL) in the prevention of graft-versus-host disease (GVHD) in recipients following allogeneic hematopoietic stem cell transplantation (allo-HSCT).MethodsRandomized controlled trials (RCTs) evaluating the safety and efficacy of SRL-based prophylaxis regimens in patients receiving allo-HSCT were obtained from PubMed, Embase, and the Cochrane database. Following specific inclusion and exclusion criteria, studies were selected and screened by two independent reviewers who subsequently extracted the study data. The Cochrane risk bias evaluation tool was used for quality evaluation, and RevMan 5.3 software was used for statistical analysis comparing the effects of SRL-based and non–SRL-based regimens on acute GVHD, chronic GVHD, overall survival (OS), relapse rate, non-relapse mortality (NRM), thrombotic microangiopathy (TMA), and veno-occlusive disease (VOD).ResultsSeven studies were included in this meta-analysis, with a total sample size of 1,673 cases, including 778 cases of patients receiving SRL-based regimens and 895 cases in which patients received non-SRL-based regimens. Our data revealed that SRL containing prophylaxis can effectively reduce the incidence of grade II–IV acute GVHD (RR = 0.75, 95% CI: 0.68∼0.82, p &lt; 0.0001). SRL-based prophylaxis was not associated with an improvement of grade III–IV acute GVHD (RR = 0.78, 95% CI: 0.59∼1.03, p = 0.08), chronic GVHD (p = 0.89), OS (p = 0.98), and relapse rate (p = 0.16). Despite its immunosuppressant effects, SRL-based regimens did not increase bacterial (p = 0.68), fungal (p = 0.70), or CMV (p = 0.10) infections. However, patients receiving SRL-based regimens had increased TMA (p &lt; 0.00001) and VOD (p &lt; 0.00001).ConclusionsThis meta-analysis indicates that addition of sirolimus is an effective alternative prophylaxis strategy for II–IV aGVHD but may cause endothelial cell injury and result in secondary TMA or VOD events.

Impact of the Inhibitory KIR-HLA Receptor-Ligand Model on Unrelated Hematopoietic Stem Cell Transplantation in Patients with Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5063-5063
Author(s):  
Jun He ◽  
Zi-xing Chen ◽  
Xiao-jing Bao ◽  
De-pei Wu ◽  
Xiao-ni Yuan ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Nk Cells ◽  
Cell Transplantation ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Receptor Ligand ◽  
Hematopoietic Stem ◽  
Ligand Model

Abstract The interaction between killer cell immunoglobin-like receptor (KIR) and HLA molecule has particular relevance to the unrelated hematopoietic stem cell transplantation (HSCT). The presence of KIR on donor’s NK cells and the absence of the corresponding KIR ligand in the recipient’s HLA repertoire as a receptor-ligand model can be used to predict the outcome of HSCT. To investigate the effect of KIR-HLA receptor-ligand mismatching and the expression of inhibitory KIR (iKIR) on the unrelated Allo-HSCT of leukemia, the following study has been carried out. The KIR genotypes of 36 patients of ALL (n=18), AML (n=10), and CML (n=8) as well as their unrelated donors were obtained from the Database of China Marrow Donor Program. KIR genotyping was performed with PCR-SSP. The KIR and HLA mismatching status (receptor-ligand mismatch model) between recipients and donors was analyzed thereafter. The expression of iKIR was determined by flow cytometry on recipients after HSCT. All cases were followed up closely until July, 2007. Among all the donor/recipient pairs analyzed, 15 pairs displayed the matched pattern with respect to the KIR genotyping though, graft-versus-host (GVH) KIR ligand-mismatched in 13 pairs, and host-versus-graft (HVG) KIR ligand-mismatched in 8 pairs. 26 recipients were lack of HLA-Cw2,4,5,6,15 ligands although iKIR/2DL1 was expressed on their corresponding donors. Similarly, 35 donors with iKIR/2DL2/L3 on their NK cells could recognized HLA- Cw1,3,7,8,12,14 ligands in their recipients. iKIR/3DL1 was expressed on 9 donors although the correlated HLA-Bw4 ligand was absent on the recipients. iKIR/3DL2 was expressed on 24 donors although the correlated HLA-A11 ligand was absent on the recipients. Except for one case, 35 patients were successfully transplanted, in which seven patients were dead, giving the survival rate of 80.0%. The cause of death was either acute/chronic GVHD or relapse. The frequency of acute GVHD (60.0%, 9/15), leading to death (26.7%, 4/15), was the highest in KIR receptor-ligand matched model. The incidence of acute GVHD and death was 30.8% (4/13) and 23.1% (3/13) in the GVH KIR ligand-mismatching, respectively; while the incidence of chronic GVHD was 37.5% (3/8) and no death happened in HVG KIR ligand-mismatching pattern. The expression of iKIR/2DL1 could be detected on ALL (13.0%∼16.6%) and CML (1.8∼6.2%) patients four month after HSCT. The expression of both iKIR/2DL1 (4%) and iKIR/2DL2 (12%) was found only in one patient with CML three month after HSCT, increased to 33.4% and 32.6% accompanied by cGVHD, and dropped to 7.6% and 10.3% one year after HSCT. These results suggested that the deficiency in iKIR/2DL1 based on the KIR-HLA receptor-ligand mismatching model together with the expression of a number of activating KIR in recipients increases the occurrence of GVHD, relapse, and death in unrelated HSCT. Analysis on KIR-HLA gene expression profiling could be useful in predicting the clinical outcome of unrelated Allo-HSCT in leukemia patients. The overall and disease-free survival after HSCT could be improved by preventing the development of GVHD.

Prospective Validation of a Chronic GvHD-Specific Proteome Pattern (cGvHD-MS14) Post Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1970-1970
Author(s):  
Eva M. Weissinger ◽  
Daniel Wolff ◽  
Jochen Metzger ◽  
Christiane E Dobbelstein ◽  
Stefanie Buchholz ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Urine Samples ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct

Abstract Abstract 1970 Introduction: Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment for many hematologic malignancies and non-malignant hematopoietic disorders, but is associated with significant morbidity and mortality with focus on acute and chronic graft-versus-host disease (GvHD). Chronic GvHD (cGvHD) occurs with increasing frequency, hampering quality of life of patients post-allogeneic HSCT and leading to increased morbidity and mortality even years after allogeneic HSCT. Diagnosis of chronic GvHD is based on clinical features and histology. Here we present the generation of cGvHD-specific proteomic pattern (cGvHD-MS14) using capillary electrophoreses and mass spectrometry to analyze urine sample collected prospectively after allogeneic HSCT. Methods: A proteomic pattern (cGvHD-MS14) was developed in order to diagnose cGvHD, to differentiate acute versus cGvHD, and to predict onset and severity of cGvHD prior to clinical diagnosis of cGVHD as a non-invasive, unbiased laboratory test for diagnosis of cGvHD. This pattern was prospectively evaluated on 329 patients (1034 urine samples) after allogeneic HSCT at MHH and 3 collaborating transplant centers. The majority of the patients had acute leukemias prior to transplantation (n=210) and were transplanted from matched unrelated or related donors (MUD n=134; MRD n=125). Reduced intensity conditioning regimens were used in about 75% of all patients and the majority (80%) received ATG (anti-thymocyte globulin) as GVHD-prophylaxis prior to transplantation and a calcineurin-inhibitor based prophylaxis afterwards. Results: Prospective and blinded evaluation revealed the correct classification of patients developing cGvHD with a sensitivity 78% and specificity of about 71% at time of diagnosis. Differentiation between late onset acute GvHD and chronic GvHD was achieved in 3 patients in this validation set. Acute GvHD prior to day 100 is not recognized by cGvHD-MS14, since aGvHD-specific peptides had been excluded during cGvHD-pattern generation. The pattern consists of 14 differentially excreted peptides, differentiating chronic GvHD from tolerant patients. Four of 14 peptides have been sequenced to date, 2 are fragments from collagen 1, 1 is from inter-alpha trypsin inhibitor heavy chain 4 and 1 is a fragment from the fibrinogen ß-chain. Conclusions: The proteomic pattern of urine proteomics enables diagnosis of cGvHD as well as differentiation of acute versus chronic GvHD. Further prospective evaluation of the cGvHD-specific pattern cGvHD-MS14 for organ specificity as well as severity prediction is currently ongoing. Taken together our results indicate that diagnosis of cGvHD is possible using CE/MS analysis of prospectively collected urine samples with high sensitivity and specificity. Disclosures: Metzger: mosaiques-diagnostics GmbH: Employment. Krons:mosaiques-diagnostics GmbH: Employment.

scholarly journals Genetic variations in the heparanase gene (HPSE) associate with increased risk of GVHD following allogeneic stem cell transplantation: effect of discrepancy between recipients and donors

Blood ◽  
2010 ◽  
Vol 115 (11) ◽  
pp. 2319-2328 ◽  
Author(s):  
Olga Ostrovsky ◽  
Avichai Shimoni ◽  
Avital Rand ◽  
Israel Vlodavsky ◽  
Arnon Nagler
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Human Leukocyte ◽  
Nucleotide Polymorphisms ◽  
Hematopoietic Stem ◽  
Mortality And Morbidity ◽  
Increased Risk

Abstract Graft-versus-host disease (GVHD) is the most common cause of nonrelapse mortality and morbidity after hematopoietic stem cell transplantation (HSCT). The well-documented involvement of heparanase in the process of inflammation and autoimmunity led us to investigate an association between HPSE gene single-nucleotide polymorphisms (SNPs) and the risk of GVHD. The present study indicates a highly significant correlation of HPSE gene SNPs rs4693608 and rs4364254 and their combination with the risk of developing acute GVHD. Moreover, the study revealed that discrepancy between recipient and donor in these SNPs may elevate significantly the risk of acute GVHD. This association was statistically significant when the recipients possessed genotype combinations dictating higher levels of heparanase compared with their human leukocyte antigen (HLA)–matched donors. In addition, HPSE gene SNPs disclosed a correlation with extensive chronic GVHD, nonrelapse mortality, and overall survival. Our study indicates involvement of heparanase in the development of acute and extensive chronic GVHD. Moreover, it suggests a possible mechanism for the aggressive behavior of T lymphocytes leading to GVHD when the recipients possess genotype combinations that dictate high levels of heparanase mRNA compared with their HLA-matched donors expressing low levels of heparanase.

scholarly journals Haploidentical Stem Cell Transplantation after Myeloabaltive Conditioning Is a Valid and Safe Option for Young Patients with Refractory or Relapsed Aggressive Non-Hodgkin Lymphoma: A Study Compared with HLA-Matched Transplant

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5849-5849
Author(s):  
Haiwen Huang ◽  
Xiaofang Xiao ◽  
Jia Chen ◽  
Zhengming Jin ◽  
Xiaowen Tang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Young Patients ◽  
Progression Free Survival ◽  
Hematopoietic Stem ◽  
Free Survival

Abstract Purpose: The role of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) therapy for refractory or relapsed (R/R) aggressive non-Hodgkin lymphoma (NHL) patients was still unknown. In this study, we aimed to explore the clinical outcome of R/R aggressive NHL patients received haplo-HSCT treatment. Patients and Methods: 23 R/R aggressive NHL patients who had undergone haplo-HSCT in our center between February 2006 and October 2015 were retrospectively analyzed, and 25 R/R aggressive NHL patients who received HLA-matched HSCT at the same period were also involved in this study. All patients received myeloablative conditioning (MAC) regimen, and antithymocyte globulin, cyclosporine A, mycophenolate mofetil and short course of methotrexate were used as graft-versus-host disease (GVHD) prophylaxis. 12 patients had experienced autologous HSCT prior to allo-HSCT. Results: The median age of the total 48 patients was 33 (16-58) years old, and there were 33 males and 15 females in the total cohorts. The diagonosis were as following: 16 (33%) diffuse large B cell lymphoma and 22 (46%) peripheral T cell lymphoma. There were no difference in sex, age at transplantation, histologic diagnosis, aaIPI score, previous ASCT and conditioning regime between HLA-matched HSCT and Haplo-hsct groups. 44 patients had achieved engrafment, and the median times to neutrophil and platelet recovery were 12 and 15 days, respectively. Incidences of grade 3-4 acute GVHD were 18.3% in haplo-HSCT group and 16.7% in HLA-matched HSCT groups(p=0.87), while 2 years cumulative incidences of chronic GVHD in these two groups were 43.5% and 36.7% (P=0.68). For 16 patients who had chemoresistant disease at transplantation in haplo-HSCT group, four patients achieved complete remission, and ten patients achieved partial remission, while the other two patients experienced disease progression at 21 days and 37 days, respectively. With a median follow-up of 25 months, 12 patients experienced disease recurrence or progression in haplo-HSCT. And four patients died of transplantation related mortality: infection (n=2); acute GVHD (n=1) and multi-organ failure (n=1). There were no differences in overall survival (OS) rate at 2 years (52.8% vs 57.0%, P=0.85) and 2 years progress free survival (PFS) rate (52.7% vs 56.9%, p=0.73) between the haplo-SCT and HLA-matched SCT groups. Multivariate analyses suggested that old age (>45 years)(p=0.02), primarychemorefractory (p=0.04)and occurrence of grade3-4 aGVHD (p=0.01) may contribute to poor prognosis. Conclusion: Haploidentical hematopoietic stem cell transplantation withmyeloablative conditioning regimenachieved satisfactory outcome with acceptable side-effects. This approachcan be a feasible and acceptabletherapy for young patients withR/R NHLwho have no access to a HLA-matched donor. Figure Comparison of outcomes after haplo-SCT and HLA-matched SCT. (a) Overall survival, (b) Progression-free survival, (c) Cumulative incidences of grade3-4 acute GVHD, (d) cumulative incidences of chronic GVHD, (e) cumulative incidences of relapse, (f) cumulative incidences of non-relapse mortality. Figure. Comparison of outcomes after haplo-SCT and HLA-matched SCT. (a) Overall survival, (b) Progression-free survival, (c) Cumulative incidences of grade3-4 acute GVHD, (d) cumulative incidences of chronic GVHD, (e) cumulative incidences of relapse, (f) cumulative incidences of non-relapse mortality. Disclosures No relevant conflicts of interest to declare.

Preliminary Experience with Haploidentical Stem Cell Transplantation for Children with Sickle Cell Disease and Stroke.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5434-5434
Author(s):  
Joseph Woodard ◽  
Winfred Wang ◽  
Raymond Barfield ◽  
Gregory Hale ◽  
Edwin Horwitz ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Sickle Cell Disease ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Sickle Cell ◽  
Chronic Gvhd ◽  
Cell Disease ◽  
Hematopoietic Stem ◽  
Cell Counts

Abstract Hematopoietic stem cell transplantation has been shown to be curative for approximately 83% of symptomatic children with sickle cell disease who have undergone the procedure. Despite these encouraging results, only 15% of children with symptoms that might merit consideration for transplantation have an available, unaffected HLA-matched sibling donor, severely limiting this therapeutic option. To address this problem, we developed a protocol for children with SCD and stroke using reduced-intensity conditioning and CD34-selected peripheral blood stem cells from haploidentical parental donors. We now report our preliminary experience using this approach in three children with SCD and stroke. After a chemotherapy-only conditioning regimen of fludarabine 150–200 mg/m2, thiotepa 10 mg/kg, i.v. busulfan targeted to a steady state concentration of 900 ng/ml, and OKT3, patients received an average of 27.2 x 106 CD34+cells/kg and 1.1 x 104 CD3+ cells/kg. Two patients required additional immunosuppression with methylprednisolone and OKT3 followed by a CD34 boost after graft rejection. One of these two had durable long-term engraftment, while one had a second rejection. Two of three patients have durable donor engraftment 20 and 24 months after transplantation, respectively. Donor T-cell chimerism evolved from predominantly host-derived to donor-derived over a number of months. One patient developed grade I acute GVHD and none developed chronic GVHD. Two engrafted patients have had no further SCD events. Both have recovery of immune function with normal CD4+ T-cell counts and normal thymic function. This preliminary experience demonstrates the feasibility of using mismatched parental donors for children with sickle cell disease. Future studies will focus on achieving reliable donor engraftment through additional graft manipulation strategies.

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