Acute myeloid leukemia with inv(3)(q21.3q26.2)/t(3;3)(q21.3;q26.2): Study of 61 patients treated with intensive protocols
Marta SitgesBlanca BoludaAna GarridoMireia MorgadesIsabel GranadaEva BarragánMontserrat ArnánJosefina SerranoMar TormoJuan BerguaMercedes ColoradoOlga SalameroJordi EsteveCelina BenaventeManuel Pérez‐EncinasRosa CollJosep‐Maria Martí‐TutusausSalut BrunetJorge SierraMiguel Á. SanzPau MontesinosJosep‐María RiberaSusana Vives
18
Citation
25
Reference
10
Related Paper
Citation Trend
Abstract:
Inv(3)(q21.3q26.2)/t(3;3)(q21.3;q26.2) is a rare poor prognosis cytogenetic abnormality present in acute myeloid leukemia (AML) and other myeloid neoplasms.The aim of this study was to evaluate the outcome of a cohort of 61 patients with newly diagnosed AML with inv(3)/t(3;3) treated with homogeneous intensive chemotherapy protocols conducted by the Spanish PETHEMA and CETLAM cooperative groups between 1999 and 2017.In this retrospective study the main clinical and biologic parameters were collected. The complete response (CR) rate, the cumulative incidence of relapse (CIR) and the overall survival (OS) were calculated. An analysis of prognostic factors for survival was performed.Sixty-one patients received induction and only 18 (29%) achieved CR (median age, 46 years). Allogeneic hematopoietic stem cell transplantation (alloHSCT) was performed in 36 patients (59%), 15 with active disease. One- and 4-year CIR were 52% and 56%. One- and 4-year OS probabilities were 41% and 13%. By multivariate analysis monosomal karyotype (MK) was associated with poorer OS (HR 2.0, P = .017).Inv(3)/t(3;3) AML is a poor prognosis entity with low response to standard chemotherapy and to alloHSCT because of frequent and early relapse. MK was associated with a poorer prognosis. Improved therapeutic strategies are clearly needed.Keywords:
Cumulative incidence
Induction chemotherapy
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.
Cumulative incidence
Hematologic disease
Cite
Citations (0)
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.
Cumulative incidence
Total body irradiation
Cite
Citations (21)
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
Cumulative incidence
Cite
Citations (0)
Both acute myeloid leukemia 1 and c‐Fos are regulatory factors of hematopoietic cell differentiation. We identified that the c‐fos promoter contains an acute myeloid leukemia 1 binding site at nucleotide positions −6–+14. c‐fos promoter activity was induced by transient overexpression of acute myeloid leukemia 1 in Jurkat T‐cells, but not by that of the short form of acute myeloid leukemia 1‐MTG8, a chimeric acute myeloid leukemia 1 protein. In 32Dcl3 myeloid cells, stable overexpression of acute myeloid leukemia 1‐MTG8 blocked the c‐fos gene transcription and cell differentiation, but that of acute myeloid leukemia did not. These data suggest that acute myeloid leukemia 1 and acute myeloid leukemia 1‐MTG8 reciprocally regulate the myeloid cell differentiation, possibly by the way of regulating c‐fos gene transcription.
RUNX1T1
IRF8
Cite
Citations (14)
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.
Cumulative incidence
Human herpesvirus 6
Cite
Citations (0)
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
Cumulative incidence
Anti-thymocyte globulin
Sirolimus
Cite
Citations (21)
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.
Cumulative incidence
Cite
Citations (29)
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.
Cumulative incidence
Cite
Citations (73)
Differentiation Therapy
Cite
Citations (31)