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 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 < 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 < 0.00001) and VOD (p < 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.

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.

Allogeneic hematopoietic stem cell transplantation in thalassemia major: results of a reduced-toxicity conditioning regimen based on the use of treosulfan

Blood ◽  
2012 ◽  
Vol 120 (2) ◽  
pp. 473-476 ◽  
Author(s):  
Maria Ester Bernardo ◽  
Eugenia Piras ◽  
Adriana Vacca ◽  
Giovanna Giorgiani ◽  
Marco Zecca ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Cumulative Incidence ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Hematopoietic Stem

Abstract Sixty thalassemia patients (median age, 7 years; range, 1-37) underwent allogeneic hematopoietic stem cell transplantation (HSCT) after a preparation combining thiotepa, treosulfan, and fludarabine. Before HSCT, 27 children were assigned to risk class 1 of the Pesaro classification, 17 to class 2, and 4 to class 3; 12 patients were adults. Twenty patients were transplanted from an HLA-identical sibling and 40 from an unrelated donor. The cumulative incidence of graft failure and transplantation-related mortality was 9% and 7%, respectively. Eight patients experienced grade II-IV acute GVHD, the cumulative incidence being 14%. Among 56 patients at risk, 1 developed limited chronic GVHD. With a median follow-up of 36 months (range, 4-72), the 5-year probability of survival and thalassemia-free survival are 93% and 84%, respectively. Neither the class of risk nor the donor used influenced outcome. This treosulfan-based preparation proved to be safe and effective for thalassemia patients given allogeneic HSCT.

Incidence and Outcome of Auto/Alloimmune Hepatitis with Hepatic Graft-Versus-Host Disease After Hematopoietic Stem Cell Transplantation.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4534-4534
Author(s):  
Michael Koldehoff ◽  
Ahmet H Elmaagacli ◽  
Reinhild Klein ◽  
Dietrich Beelen
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Graft Versus Host Disease ◽  
Chronic Gvhd ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host

Abstract Abstract 4534 Auto/alloimmune hepatitis (AIH) is an inflammatory liver disease characterized histological by a dense mononuclear cell infiltrate in the portal tract and serological by the presence of non-organ and liver-specific antibodies, high transaminases and increased levels of IgG. The relation between allogeneic hematopoietic stem cell transplantation (HSCT) and auto/alloimmune disease is complex. To examine this association, we retrospectively studied 1,636 allogeneic patients (median age 43, range 18–73 years) between May 1996 and December 2008. Among these patients, 311 (19%) developed hepatic graft-versus-host disease (GvHD) (162 pts had a hepatic GvHD of grade > II). We followed 25 patients (11 male, 14 female) in whom GvHD of the liver presented with marked elevation of serum aminotransferases, clinically resembling acute hepatitis and auto/antibodies characteristics for AIH. The median age at transplant was 35 (range, 18–54) years. Onset of liver dysfunction was at 286 days (range, 55–2766) after HSCT. Median peak serum was 312 (range 105–1750) U/L for alanine aminotransferase, 629 (133-2410) U/L for gamma-glutamyl transferase and 1.74 (0.5-23.4) mg/dl for bilirubin. The autoantibody profiles of AIH were 60% for anti-nuclear antibody, 44% for antibodies to liver-kidney microsomes, 24% for antibodies to smooth-muscle antigens, 28% for anti-mitochondrial antibody, 16% for antibodies to actin, 8% for antibodies to nucleoli, and 4% for other autoantibodies. AIH had a higher prevalence in younger and in female patients. AIH occurred in 92% in patients, who were transplanted with G-CSF mobilized and peripherally collected stem cells (PSC), but in only 8% in patients with bone marrow (BM) source (p<0.02), comparing all transplanted patients (1326 PSC, 310 BM). Stem cell grafts from matched sibling donor or matched unrelated donor were similar in the two groups. Acute GvHD of grade> II occurred more frequently in the groups with AIH (15/25 vs. 649/1636, p<0.002), and chronic GvHD (11 limited, 14 extensive) was ascertained in all AIH patients vs. 49.8% in all transplanted patients (p<0.0001). Three patients with AIH died from pulmonary bleeding, chronic GvHD, and relapse, whereas 22 patients with AIH are still alive (88%) at a median survival time of 2570 days. In conclusion, our evaluation confirms a strong association between G-CSF mobilized PSC, chronic GvHD and the development of AIH. 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.

The Use of Imatinib with Chemotherapy and Allogeneic Hematopoietic Stem Cell Transplantation Improves Survival of Philadelphia Positive Acute Lymphoblastic Leukemia in Adults

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3653-3653
Author(s):  
Josefina Perez-Nuñez ◽  
Antonio Jimenez-Velasco ◽  
Katy Hurst ◽  
Manuel Barrios-Garcia ◽  
MJ Moreno ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Lymphoblastic Leukemia ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct

Abstract Philadelphia positive acute lymphoblastic leukemia (Ph + ALL) accounts for approximately 20% -30% of all adult ALL. The prognosis of patients with Phi + ALL is unfavorable when treated with standard chemotherapy schemes, presenting a long-term survival of 15% -20%. Since the introduction of Imatinib (IM) to treatment regimens the survival of these patients has improved, although allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative option. We conducted a retrospective analysis of Ph + ALL patients before and after IM became available in order to analyze the impact of IM on survival in adult Phi + ALL. Patients and methods Between April 1997 and April 2013 we diagnosed 120 over 15 year old patients with ALL (B and T lineage), 31 (25.8%) of which were Phi +, all B lineage. Of these 31 cases, 30 were treated with protocols from Spanish group PETHEMA with curative intent. 14 of them (47%) were treated with chemotherapy and Imatinib (IM cohort) and 16 (53%) with chemotherapy (pre-IM cohort). In 17 of the 30 cases allogeneic HSCT was performed, 7 in the pre-IM cohort and 10 in the IM cohort. In the post-transplant period, two patients were treated with Dasatinib due to positive minimal residual disease (BCR-ABL1 positive). The probabilities of overall survival (OS) (death) and event free survival (EFS) (no response, relapse or death) were estimated using the Kaplan-Meier product limit method. Differences between groups were tested using the X2 test. Univariate analysis was performed using Cox regression models or log-rank test. Multivariate analysis was performed using Cox proportional hazards regression model. The study was conducted in accordance with the Declaration of Helsinki. Results The median age was 38 years (range, 15-66 years), 17 patients were males and 13 females. The whole series survival was 32.4 ± 9.2%. The OS mean of the pre-IM cohort was 3.1 years (CI 95%, 0.5-5.7) and 6.9 years (CI 95%, 4.4-9.4) in the IM cohort (figure 1). The main characteristics of both groups are reflected in Table 1. When we analyzed the EFS, the variables that influenced it were being treated with IM (48% in the IM cohort versus 12.5% in the pre-IM cohort, p = 0.03), having received an allogeneic HSCT (45% versus 8%, p = 0.004) and being in first complete remission before allogeneic HSCT (51% versus 0%, p <0.001). In the analysis of OS, the only variables with prognostic significance were: treatment with IM (63% in the IM cohort versus 12.5% in the pre-IM cohort, p = 0.01) and having received an allogeneic HSCT (55 % versus 0%, p <0.001). When the 17 patients that received allogeneic HSCT were analyzed separately, OS in the pre-IM cohort was 29 ± 17% versus 79 ± 13% in the IM cohort (p = 0.057). Table 1. Patient characteristics (N=30) Characteristic Pre-IM cohort(N=16) IM cohort(N=14) P Female/Male 7/9 6/8 0.96 Age ² 40 years 12 (75%) 10 (71%) 0.82 ³ 50 x109/L WBC 8 (50%) 4 (29%) 0.23 Transcript type: e1a2 b2a2/b3a2 12 (75%) 4 (25%) 11 (79%) 3 (21) 0.83 Morphological CR after induction 13/15 (88%) 13/13 (100%) 0.17 No. of Allo-HSCT 7 (44%) 10 (71%) 0.13 CR pre Allo-HSCT: 1CR 2CR 5 (71%) 2 (29%) 10 (100%) 0 (0%) 0.07 Relapse 8/13 (61.5%) 4/13 (31%) 0.12 Exitus 14 (87.5%) 5 (36%) 0.003 Abbreviations: IM, imatinib. WBC, white blood cells. CR, complete remision. Allo-HSCT, allogenetic hematopoietic stem cell transplantation. Figure 1 Figure 1. Conclusions In our study we show how adult Phi + ALL patients who are treated with chemotherapy associated with IM and subsequently receive an allogeneic HSCT exhibit a higher overall survival rate than those treated in the pre-IM era. Although Phi + ALL is still considered of very high risk, in our series of patients treated in the IM era, with a follow-up of over 7 years, overall survival was of 63%, higher than that of historical series of adults with Phi negative ALL. This work has been financed by a grant from the Malaga Association for Research in Leukemia "AMPILE" and the FIS 11-01966 project. Disclosures No relevant conflicts of interest to declare.

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