Disease Status Is the Major Prognosis Factor for Allogenic Transplantation Outcome for Hodgkin Lymphoma: a Retrospective Study From the French Society of Bone Marrow Graft Transplantation and Cellular Therapy (SFGM-TC)
Ambroise MarçaisKarin BilgerRaphaël PorcherMarie RobinMohamad MohtyMauricette MichaletDidier BlaiseStéphane VigourouxPierre BordigoniPatrice CéballosÉric DeconinckNathalie DehdinBernard RioJacques‐Olivier BayCécile PautasFrédéric GarbanNorbert IfrahFelipe SuárezGaëlle GuillermNathalie ContentinJean BourhisMarc BernardJérôme CornillonAnne HuynhIbrahim Yakoub‐AghaAnne SîrventL FouillardAgnès Buzyn
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Cumulative incidence
Autologous stem-cell transplantation
Allogeneic hematopoietic stem cell transplantation (HSCT) is an important therapy option for children with acute myeloid leukemia (AML) resistant to the first course of induction chemotherapy (IC1st). We aimed to identify the efficacy of unmanipulated haploidentical HSCT (haplo-HSCT) in children with AML in the first complete remission and whether children resistant (IC1st-resistant; n = 38) or sensitive (IC1st-sensitive; n = 59) to the IC1st can achieve comparable outcomes. The cumulative incidence of grades III to IV acute graft-versus-host disease (GVHD) and severe chronic GVHD was .0% versus 20.1% (P = .038) and 21.7% versus 13.2% (P = .238), respectively, for the IC1st-resistant and IC1st-sensitive groups. The 3-year cumulative incidence of relapse and nonrelapse mortality was 22.2% versus 7.6% (P = .061) and 5.3% versus 10.8% (P = .364), respectively, for the IC1st-resistant and IC1st-sensitive groups. The 3-year probability of overall survival and disease-free survival was 76.3% versus 83.0% (P = .657) and 72.5% versus 81.6% (P = .396), respectively, for the IC1st-resistant and IC1st-sensitive groups. Multivariate analysis failed to show significant differences in survival rates between the groups. Thus, our results show that unmanipulated haplo-HSCT may overcome the poor prognostic significance of IC1st-resistance in children with AML, and it is valid as a postremission treatment for children with IC1st-resistant AML lacking an HLA-matched donor.
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Abstract Nucleoporin 98 ( NUP98 ) gene rearrangements comprise a family of rare recurrent alterations in acute myeloid leukemia (AML), and conferred dismal outcomes. The efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) were still unclear. In this retrospective, multicenter, real-world study, we enrolled 26 de novo adult AML patients with NUP98 rearrangements who received first allo-HSCT. The 100-day cumulative incidence of grade II–IV acute graft-versus-host disease (GVHD) after allo-HSCT was 19.2% (95% CI, 3.8–34.7%) and the 2-year cumulative incidences of moderate to severe chronic GVHD after allo-HSCT was 47.5% (95% CI, 17.0–77.9%). Ten (38.5%) patient received maintenance therapies after allo-HSCT. Among the 24 patients with MRD monitoring regularly, all of them achieved MRD negative after allo-HSCT, and 21 (87.5%) achieved persistent MRD negative until the last follow-up. The 2-year cumulative incidence of relapse and non-relapse mortality after allo-HSCT was 17.2% (95% CI, 1.4–33.1%) and 4.6% (95% CI, 0–13.7%), respectively. The 2-year probabilities of leukemia-free survival and overall survival after allo-HSCT were 78.2% (95%CI, 62.8–97.2%) and 86.3% (95%CI, 73.0–100%), respectively. In summary, we firstly identify the efficacy and safety of allo-HSCT in adult AML patients with NUP98 rearrangement, which should be further confirmed in prospective cohorts with a longer follow-up.
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Objective To analyze the incidence of herpes zoster(HZ) after allogeneic hematopoietic stem cell transplantation (HSCT) and its effect on 1-year survival.Methods The medical records of 96 patients undergoing HSCT in Department of Hematology of Guangzhou General Hospital of Guangzhou Military Command during January 2003 and December 2010 were reviewed. Results HZ was identified in 7 of the 96 patients within 1 year after transplantation with a cumulative incidence of 7.3%.The median time to onset after HSCT was 70(range 50-290) days and the median duration of HZ was 10(range 7-180) days.The severity of graft versus host disease(GVHD),intensified treatment of GVHD and regular prevention with acyclovir were associated with the incidence of HZ.Kaplan-Meier survival analysis indicated that HZ had no effect on the 1-year survival of patients(P = 0.87).Conclusions Post-HSCT HZ is a common complication.Severe GVHD,intensified treatment of GVHD and no regular prevention with acyclovir are associated with higher incidence of HZ,but 1-year survival of the patients is not affected by HZ.
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Hematology
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To evaluate the efficacy and safety of haploidentical (from family member donors) hematopoietic stem cell transplantation (HSCT) for children with hematologic malignancies.Fifty-eight children under fourteen years with hematological malignancies underwent haploidentical HSCT. All patients had poor-risk clinical or cytogenetic features and reclassified into high-risk and standard-risk groups. Transplantation outcomes were analyzed.Of fifty-eight patient/donor pairs, seven (12.1%) were mismatched in two HLA loci, twenty (34.5%) in three loci, and thirty-one (53.4%) in four loci. Follow-ups were performed for a median of 1,663 (752-2,664) days after transplantation. All patients achieved stable engraftments. The cumulative incidence of acute graft-versus-host disease (GVHD) of grades 2-4 was (54.8+/-7.6)%, and that of grades 3-4 was (11.4+/-4.8)%. The cumulative incidence of chronic GVHD was (45.6+/-7.8)% for the total and (19.6+/-6.5)% for the extensive. Thirty-eight patients survived with a 2-year actual overall rate of survival 59.0% and 78.9% in the high-risk and standard-risk group, respectively. The 3-year probability of LFS was (58.6+/-8.0)% and (68.4+/-10.7)%, respectively.The results encourage extending haploidentical HSCT without T-cell depletion treatments to children with an indication for transplantation.
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Hematologic disease
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A retrospective study was conducted among Italian children treated with hematopoietic stem cell transplant (HSCT) to evaluate the incidence and risk factors in the development of osteochondroma (OC). OC occurred in 27 patients who received autologous or allogeneic HSCT. The estimated 5-, 10-, and 15-year cumulative risk of developing OC was 0.5%, 3.2%, and 6.1%, respectively. Analysis of cumulative risk stratified by the various risk factors revealed that male sex (P=.026), autologous HSCT (P=.001), age at HSCT (< or =3 years) (P < .0001), and total body irradiation (TBI) (P <.0001) significantly affected the risk of OC. Multivariate analysis, restricted only to tumor types with at least 1 case of OC, showed that earlier age at HSCT (P =.0004) and TBI (P < .0001) were the only factors that were significantly associated with OC.
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Total body irradiation
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Objective
To compare the efficacy of haploidentical hematopoietic stem cell transplantation (HSCT) and HLA-identical transplantation for hematologic diseases, and analyze risk factors related to overall survival (OS).
Methods
There were 81 patients with hematological malignancies receiving Allo-HSCT from October, 2011 to July, 2017. The patients were divided into two groups: 30 patients undergoing haploidentical HSCT and 51 cases undergoing matched sibling donor HSCT (MSD-HSCT). Implantations of hematopoietie stem cells, incidence of graft versus host disease (GVHD), OS rate, disease free survival (DFS) rate, incidence of relapse and non-relapse-mortality were analyzed statistically. Multivariate analysis was used to analyze the risk factors related to OS.
Results
All patients achieved sustained engraftment. 100 days after Allo-HSCT, the cumulative incidence for Ⅱ-Ⅳ aGVHD had no significant difference between haplo-HSCT and MSD-HSCT (56.7% versus 11.8%, P=0.000). There was no significant difference in the 1-year cumulative incidence for cGVHD between haplo-HSCT and MSD-HSCT (20.6% versus 45%, P=0.341). The 2-year OS rate in patients receiving haplo-HSCT and MSD-HSCT was 63.2% and 78.4% respectively (P=0.078). The 2-year DFS rate in patients receiving haplo-HSCT and MSD-HSCT was 54.8% and 66.9% respectively (P=0.159). The 2-year relapse and non-relapse-mortality rate in patients receiving haplo-HSCT and MSD-HSCT was 25.9% and 24%, and 22.9% and 9.5% respectively. There were no statistically significant differences in relapse rate and mortality between two groups (P=0.465, 0.118). Multivariate analysis showed that relapse and Ⅱ-Ⅳ aGVHD were independent prognostic indictors for OS with relative risk 6.671 (95% CI 2.791-15.946) and 3.073 (95% CI 1.296~7.284) (P<0.05).
Conclusion
The therapeutic effects of haploidentical transplantation were similar to those of HLA-identical sibling transplantation. Relapse and Ⅱ-Ⅳ aGVHD after transplantation have prognostic significance for the long-term survival of transplant patients.
Key words:
hematopoietic stem cell transplantation; Hematopathy; Prognosis
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To study the potential relationship between HHV-6 activation and acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic cell transplantation (HSCT).Peripheral blood samples were collected before and weekly after HSCT from 72 consecutive recipients. HHV-6 DNAemia was monitored by nested polymerase chain reaction (PCR). The genotypes of HHV-6 were identified by Hind III restriction assay.Of the 72 patients, HHV-6 DNAemia were detected in 45 (62.5%) on a median of day 14 (range, 7 - 63 days) after HSCT. Grade I - IV aGHVD occurred in 40 (55.6%) on a median of day 26 (range, 9 -73 days). The median onset time of HHV-6 DNAemia was significantly earlier than that of aGHVD (P = 0.018). Compared with that in HHV-6 DNAemia negative [HHV-6(-)] patients, the cumulative incidence of grade I - IV aGHVD was higher (68.9% vs. 33.3% , P = 0.003) in HHV-6 (+) patients. Cumulative incidence of grade II - IV aGVHD in HHV-6 (+) cohort was also higher than that in HHV-6 (-) cohort (35.6% vs 14.8% , P = 0.027). Cumulative incidence of grade I - IV aGVHD was higher in patients with both HHV-6 and CMV positive (CMV+/HHV-6+) than in those with either CMV (CMV+/HHV-6-) or HHV-6 positive (CMV+/HHV-6+) and neither of them positive (CMV-/HHV-6-) [78.9% (30/38), 55. 6% (5/9) , 14. 3% (1/7) and 22. 2% (4/18), respectively, P = 0. 0001]. Cumulative incidence of grade II - IV aGVHD in CMV+/HHV-6+ group was also higher than that in CMV+/HHV-6-, CMV-/HHV-6+ and CMV-/HHV-6- groups [42.1% (16/38), 22.2% (2/9), 0% (0/7) and 11.1% (2/18), P = 0. 008].Patients with HHV-6 activation or HHV-6/CMV co-infection maybe involved in the occurrence of aGVHD after HSCT.
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Human herpesvirus 6
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Acute graft-versus-host disease (aGVHD) is a major cause of morbidity and mortality in patients undergoing unrelated hematopoietic stem cell transplantation. We prospectively evaluated the efficacy of intermediate-dose rabbit anti-thymocyte globulin (Thymoglobulin® a total of 4.5 mg/kg given over days −3, −2, and −1) in combination with tacrolimus and sirolimus for the prevention of aGVHD. We enrolled 47 recipients who underwent unrelated hematopoietic stem cell transplantation. Patients received daily granulocyte colony-stimulating factor starting on day +6 until neutrophil engraftment (median duration, 11 days; range, 9-15 days). Twenty-two patients received HLA 8/8 and 25 received 7/8 matched grafts, respectively. The median follow-up duration was 23.6 months (range, 18.8-27.9 months). The cumulative incidence of grade II to IV aGVHD was 23.4% (95% confidence interval, 12.4-36.3). At 2-year follow-up, the cumulative incidence of nonrelapse mortality was 31.9%, cumulative incidence of relapse was 24.6%, and cumulative incidence of chronic GVHD was 33%. Progression-free survival at 1 year was 54%, with a median of 17.7 months. Overall survival at 1 year was 65%, with no median reached. These results suggest that the combination of Thymoglobulin, tacrolimus, and sirolimus in patients undergoing unrelated hematopoietic stem cell transplantation is well tolerated and associated with a low incidence and severity of aGVHD and chronic graft-versus-host disease. Acute graft-versus-host disease (aGVHD) is a major cause of morbidity and mortality in patients undergoing unrelated hematopoietic stem cell transplantation. We prospectively evaluated the efficacy of intermediate-dose rabbit anti-thymocyte globulin (Thymoglobulin® a total of 4.5 mg/kg given over days −3, −2, and −1) in combination with tacrolimus and sirolimus for the prevention of aGVHD. We enrolled 47 recipients who underwent unrelated hematopoietic stem cell transplantation. Patients received daily granulocyte colony-stimulating factor starting on day +6 until neutrophil engraftment (median duration, 11 days; range, 9-15 days). Twenty-two patients received HLA 8/8 and 25 received 7/8 matched grafts, respectively. The median follow-up duration was 23.6 months (range, 18.8-27.9 months). The cumulative incidence of grade II to IV aGVHD was 23.4% (95% confidence interval, 12.4-36.3). At 2-year follow-up, the cumulative incidence of nonrelapse mortality was 31.9%, cumulative incidence of relapse was 24.6%, and cumulative incidence of chronic GVHD was 33%. Progression-free survival at 1 year was 54%, with a median of 17.7 months. Overall survival at 1 year was 65%, with no median reached. These results suggest that the combination of Thymoglobulin, tacrolimus, and sirolimus in patients undergoing unrelated hematopoietic stem cell transplantation is well tolerated and associated with a low incidence and severity of aGVHD and chronic graft-versus-host disease.
Thymoglobulin
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Anti-thymocyte globulin
Sirolimus
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Objective: To evaluate the efficacy and safety of haploidentical (from family member donors) hematopoietic stem cell transplantation (HSCT) for children. Patients and methods: Fifty-eight children under fourteen years old with hematological malignancies underwent haploidentical HSCT. Outcomes were analyzed. Results: Of Fifty-eight patient/donor pairs, seven (12.1%) were mismatched in two HLA loci, twenty (34.5%) in three loci, and thirty-one (53.4%) in four loci. Follow-ups were performed for a median of 915 (227-1898) days after transplantation. All patients achieved stable engraftments. The cumulative incidence of acute graft-versus-host disease (GVHD) of grade 2-4 was 54.8%7.6%, and that of grade 3-4 was 11.4%4.8%. The cumulative incidence of chronic GVHD was 45.6%7.8% for total and 19.6%6.5% for extensive. Fourty patients survived with a 3-year probability of leukemia-free survival (LFS) 44.7%13.9%. Eighteen patients died, five from infection, eight from relapse of leukemia, two from heart failure, two from GVHD, and one from lymphoproliferative disorders. Conclusion: The results encourage extending haploidentical HSCT without T-cell depletion treatments to children with an indication for transplantation. Objective: To evaluate the efficacy and safety of haploidentical (from family member donors) hematopoietic stem cell transplantation (HSCT) for children. Patients and methods: Fifty-eight children under fourteen years old with hematological malignancies underwent haploidentical HSCT. Outcomes were analyzed. Results: Of Fifty-eight patient/donor pairs, seven (12.1%) were mismatched in two HLA loci, twenty (34.5%) in three loci, and thirty-one (53.4%) in four loci. Follow-ups were performed for a median of 915 (227-1898) days after transplantation. All patients achieved stable engraftments. The cumulative incidence of acute graft-versus-host disease (GVHD) of grade 2-4 was 54.8%7.6%, and that of grade 3-4 was 11.4%4.8%. The cumulative incidence of chronic GVHD was 45.6%7.8% for total and 19.6%6.5% for extensive. Fourty patients survived with a 3-year probability of leukemia-free survival (LFS) 44.7%13.9%. Eighteen patients died, five from infection, eight from relapse of leukemia, two from heart failure, two from GVHD, and one from lymphoproliferative disorders. Conclusion: The results encourage extending haploidentical HSCT without T-cell depletion treatments to children with an indication for transplantation.
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To investigate the efficacy and safety of haploidentical (from family member donors) hematopoietic stem cell transplantation (HSCT) for children. 42 children under 14 yrs old with hematological malignancies underwent haploidentical HSCT. Outcomes were analyzed. Thirty-three children were classified as high-risk candidates. Of 42 patient/donor pairs, 4 (9.5%) were mismatched in 2 HLA loci, 15 (35.7%) in 3 loci, and 23 (54.8%) in 4 loci. Follow-ups were performed for a median of 1110 (449-1959) days after transplantation. All patients achieved stable engraftments. The cumulative incidence of acute graft-versus-host disease (aGVHD) of grade 2-4 was 57.2%, and that of grade 3-4 was 13.8%. The cumulative incidence of chronic graft-versus-host disease (cGVHD) was 56.7% for total and 29.5% for extensive. Twenty-seven patients survived with a 3-yr probability of leukemia-free survival (LFS), 57.3+/-8%, 18 of them were in the high-risk group. Fifteen patients died, 4 from infection, 7 from relapse of leukemia, 2 from heart failure, one from severe aGVHD, and one from lymphoproliferative disorders. The results encourage extending haploidentical HSCT without T cell depletion treatments to children with an indication for transplantation.
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