The t(9;11) Confers Good Prognosis in AML Patients Treated with Stem Cell Transplantation As Compared to Non-t(9;11) and Other Adverse-Risk Abnormalities

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2527-2527
Author(s):  
Claudia Ulrike Walter ◽  
Fahed Almhareb ◽  
Naeem A. Chaudhri ◽  
Abu Jafar Saleh ◽  
Wahiba Chebbo ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Risk Group ◽  
Intermediate Risk ◽  
Hematopoietic Stem ◽  
Mll Gene ◽  
Significant Difference ◽  
First Remission ◽  
11Q23 Abnormalities

Abstract Abstract 2527 Background: In contrast to most translocations affecting the MLL gene, the t(9;11) is not associated with a markedly poor prognosis. Several studies revealed a very favorable outcome in the pediatric patient group. In adult AML, the t(9;11) has also been associated with superior survival, at least compared to other 11q23 abnormalities. Therefore, 11q23 rearrangements in adult AML are now often dichotomized into t(9;11) and non-t(9;11), with the former being included in the intermediate-risk group and the latter in the adverse-risk group. The proposed European Leukemia Net (ELN) cytogenetic reporting criteria reflect this division. We investigated whether the outcome of AML patients treated with allogeneic hematopoietic stem cell transplantation (HSCT) with t(9;11) remains significantly different from the rest of the adverse-risk cytogenetic group. Methods: Conventional cytogenetics and FISH data from diagnostic bone marrow of 110 adult AML patients treated with HSCT was reviewed and patients classified according to the recommendations of the European Leukemia Net and included 32 with favorable risk, 60 in the intermediate-risk group, and 18 in the adverse-risk group. FISH confirmed MLL rearrangement in cases with apparent 11q23 abnormalities. We compared outcome of patients with t(9;11) to the group of patients with adverse-risk cytogenetics that included all MLL-positive non-t(9;11) among other cytogenetic abnormalities classified adverse-risk. Our study included 62 (56%) patients treated in first remission (CR1), while most non-CR1 AML patients were treated with HSCT in CR2. Patients were between 14 and 57 years, with median age of 25 years. Results: Of the 110 AML patients, 9 (8%) had MLL gene rearrangement. Of these patients only 5 (4.5% of all patients) had t(9;11). When all patients with MLL rearrangement were considered, there was no significant difference between this group and the patients with adverse-risk cytogenetics in overall survival (OS) or event-free survival (EFS). In contrast, when only patients with the t(9;11) were considered, the t(9;11) patients had significantly longer OS (P=0.02) and EFS (P=0.03) as compared with patients with adverse cytogenetics including all non-t(9;11) MLL-rearranged cases. The outcome of MLL-positive non-t(9;11) patients was similar to the group with adverse-risk cytogenetics. MLL rearrangements in the non-t(9;11) group included t(4;11)(q21;q23), t(6;11)(q27;q23) and a variant t(6;11;7)(q27;q23;q11.2), as well as t(11;17)(q23;q25). The survival for patients with t(9;11) remained significantly longer even when only patients treated with HSCT in first remission were considered, although numbers were small. All five patients with t(9;11) were treated with HSCT in CR1. Conclusions: The data supports the conclusion that MLL-positive t(9;11) AML patients should be classified differently from the rest of the MLL-rearranged cases and should be considered as part of the intermediate-risk group. This classification separating the t(9;11) cases from the rest of the MLL-positive cases should be maintained even when patients are treated with allogeneic HSCT. Disclosures: No relevant conflicts of interest to declare.

Application of Risk-Adapted Therapy for Acute Myeloid Leukemia to a Population. Effects of Stem Cell Transplantation on Outcome.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4449-4449
Author(s):  
Anders Wahlin ◽  
Mats L. Brune ◽  
Rolf Billstrom
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Risk Group ◽  
Low Risk ◽  
Intermediate Risk ◽  
Relapse Free Survival ◽  
Free Survival ◽  
First Remission

Abstract We introduced a risk-adapted treatment program for non-APL AML in four Swedish health regions. The aim was to optimise treatment results by the use of risk group stratification, mainly based on cytogenetic findings at diagnosis. All patients received induction therapy with idarubicin-cytarabine 3+7 and consolidation cycles containing high-dose cytarabine. Stem cell transplantation was done in CR1 in selected patients, sparing patients with low/intermediate risk of relapse the risks associated with transplantation. 279 patients, 77% of all AML patients 18–60 years (median 51 yrs), in the population were included in the program. Cytogenetics was performed in 98%. Excluding APL, 19 patients had low-risk. The intermediate-risk group consisted of 165 patients, 96 with a normal karyotype. 95 patients were allocated to the high-risk group. 6% died < 30 days after diagnosis. CR rate was 80%. 111 transplants, 78 allogeneic/URD and 33 autologous, were performed in CR1. 40% of all patients were alive after five years. Median overall survival time was 887 days in low-risk, 611 days in intermediate risk, 345 days in high-risk patients. Relapse-free survival times were also significantly (p<0.001) different between the three risk groups. 43% of responding patients were alive in first remission after four years. 4-year relapse-free survival was significantly better for both intermediate risk (67%) and high-risk (41%) with allogeneic/URD transplantation than with autologous transplant or chemotherapy alone. Relapse was observed more often among patients treated with chemotherapy alone (42%, p=0.03) or with autologous transplants (42%, p=0.09) than among patients receiving allogeneic/URD transplants in CR1, 22%. Our results do not support the use of autologous transplantation in AML in first remission.

Validation of Proposed European Leukemia Net Recommendations for Standardized Reporting and Classification of Cytogenetic Risk in AML Patients Treated with Stem Cell Transplantation

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4894-4894
Author(s):  
Claudia Ulrike Walter ◽  
Fahed Almhareb ◽  
Naeem A. Chaudhri ◽  
Wahiba Chebbo ◽  
Shad Ahmed ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Risk Stratification ◽  
Risk Group ◽  
Intermediate Risk ◽  
Event Free Survival ◽  
Free Survival ◽  
Significant Difference ◽  
First Remission

Abstract Abstract 4894 Background: Pretreatment karyotypes of leukemic cells provide the core for risk-stratification schemes in acute myeloid leukemia (AML) and cytogenetic abnormalities are well established as the strongest prognostic factor for response to therapy and for survival in AML patients. Several cytogenetic risk classifications have been built to stratify AML patients. Only the recent European Leukemia Net (ELN) recommendations by an international panel proposed a new standardized cytogenetic reporting system for AML. More importantly, few studies attempted so far to validate the ELN requirements for risk assessment in AML patients treated with allogeneic hematopoietic stem cell transplantation (HSCT). We investigated whether our series of adult AML patients treated with HSCT could validate the ELN classification criteria. We also assessed the prognostic value of this new risk stratification scheme. Methods: ELN cytogenetic reporting criteria were applied to a series of 110 adult AML patients from a single institution in the Middle East for whom complete cytogenetic data from pretreatment leukemic marrow were available and patients were assigned to the proposed cytogenetic risk subgroups, accordingly. We compared outcome for the different prognostic subgroups. Parameters analyzed were overall survival (OS) and event-free survival (EFS). Our AML group included 62 (56%) patients treated in their first remission (CR1), while most non-CR1 AML patients were treated with HSCT in CR2. The median age of all patients was 25 years (range: 14–57). Results: The patient group included 32 (29%) patients with favorable risk, 60 (55%) in the intermediate-risk group, and 18 (16%) in the adverse-risk group. When all the three groups were considered, there was significant difference in overall survival (OS) (P=0.007) and event-free survival (EFS) (P=0.007). However, there was no significant difference between our favorable-risk group and the intermediate-risk group. This is most likely due to selection bias in the favorable group (e.g. CD56 expression and other unfavorable markers). The adverse-risk group had significantly (P=0.002) shorter survival with median survival of 7.5 months vs. the intermediate-risk group where median survival has not been reached with an average follow-up of 46 months. When we attempted to consider only patients treated with HSCT in the first remission, there were too few patients in the intermediate-risk group (7 patients) for statistical evaluation. Conclusions: The ELN criteria proofed valuable in risk-stratifying our set of adult AML patients who were treated with HSCT and represent a Middle Eastern population. Our series clearly validated the ELN classification. The ELN classification needs further validation in patients treated with HSCT in first remission. Disclosures: No relevant conflicts of interest to declare.

Trisomy 8 Remains An Intermediate Cytogenetic Risk Factor in Patients with Acute Myeloid Leukemia (AML) Treated with Stem Cell Transplantation

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4900-4900
Author(s):  
Claudia Ulrike Walter ◽  
Fahed Almhareb ◽  
Naeem A. Chaudhri ◽  
Hazzaa Al Zahrani ◽  
Mohammad Bakr ◽  
...  
Keyword(s):  
Risk Factor ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Conflicts Of Interest ◽  
Risk Group ◽  
Risk Groups ◽  
Intermediate Risk ◽  
Trisomy 8 ◽  
Hematopoietic Stem

Abstract Abstract 4900 Background: Trisomy 8 is the most common chromosomal change in AML, as sole aberration in 5 % of cytogenetically abnormal cases and occurring together with other abnormalities in an additional 10% and little is known about the pathogenetic impact of trisomy 8. Most studies reported trisomy 8 in AML to be associated with intermediate risk. However, some reports have identified a poorer outcome than is usually seen in the intermediate group, considering trisomy 8 an adverse prognostic factor. More importantly, the clinical behavior and outcome of patients with trisomy 8 who are treated with hematopoietic stem cell transplantation (HSCT) is not known. We investigated the outcome in patients with trisomy 8 who were treated with HSCT. Methods: Bone marrow conventional cytogenetic and FISH data from 110 adult AML patients was reviewed and patients divided into three cytogenetic risk groups according to the European LeukemiaNet reporting system while separating patients with trisomy 8 into another, fourth, independent group. Patients with trisomy 8 as part of a complex karyotype (complex = 3 or more abnormalities) were excluded. We also compared outcome of patients with trisomy 8 to the intermediate-risk group alone and adverse-risk group alone, respectively. The AML cohort included 62 (56%) patients treated in their first remission (CR1) while most non-CR1 AML patients were treated with HSCT in CR2. The median age of all patients was 25 years (range: 14–58). Results: Patients with trisomy 8 were 9 (8%). Patients with trisomy 8 showed significantly longer overall survival (OS) (P=0.02) and event-free survival (EFS) (P=0.03) as compared to patients with adverse cytogenetics. The outcome of trisomy 8-positive patients was similar to the intermediate-risk group. Conclusions: This data suggests that trisomy 8 in AML is an intermediate-risk factor when patients are treated with HSCT. While we did not compare the outcome of HSCT with the outcome of trisomy 8-positive patients treated with intensive chemotherapy, most likely the cytogenetic risk of trisomy 8 for patients after HSCT is similar to their cytogenetic risk when treated with chemotherapy. Disclosures: No relevant conflicts of interest to declare.

Rearrangements of 12p in Acute Myeloid Leukemia (AML) Remain a Significant Adverse Prognostic Marker When Patients Are Treated with Stem Cell Transplantation

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4464-4464
Author(s):  
Claudia Ulrike Walter ◽  
Fahed Almhareb ◽  
Naeem A. Chaudhri ◽  
Hazzaa Al Zahrani ◽  
Wahiba Chebbo ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Chromosomal Abnormalities ◽  
Conflicts Of Interest ◽  
Hematopoietic Stem ◽  
Intermediate Group ◽  
The Poor ◽  
Significant Difference ◽  
First Remission

Abstract Abstract 4464 Background: Alterations of the short arm of chromosome 12, most often resulting in loss of chromosomal material, are a recurrent feature in myeloid malignancies and occur in about 5 % of cytogenetically abnormal AML. Chromosomal abnormalities of 12p in AML have been reported to be associated with a non-favorable outcome. However, it is unclear how dismal the outcome is, as AML with 12p abnormalities is variably included in the intermediate or poor prognosis groups. Moreover, the role of allogeneic hematopoietic stem cell transplantation (HSCT) on outcome of patients with 12p abnormalities is not known. We investigated whether HSCT can improve the poor survival of patients with 12p abnormalities. Method: Bone marrow conventional cytogenetic and FISH data from 110 adult AML patients was reviewed and patients were divided into three cytogenetic risk groups according to the European LeukemiaNet reporting system while separating the patients with 12p aberrations into one independent fourth group. We also compared outcome of the 12p group with to the intermediate group alone or after combining intermediate with favorable, since there was no significant difference between the favorable and the intermediate groups. The AML cohort included 62 (56%) patients treated in their first remission (CR1) while most non-CR1 AML patients were treated with HSCT in CR2. The median age of all patients was 25 years (range: 14–58). Result: Patients with 12p abnormalities were 4 (4%). Patients with 12p abnormalities had a significantly shorter overall survival (OS) (P=0.03) and event-free survival (EFS) (P=0.04). Their outcome was similar to the adverse-risk cytogenetic group, and survival was significantly shorter than in the intermediate group (P=0.02). The poor outcome was significant even when only patients treated with HSCT in first remission were considered. All four patients with 12p abnormalities were treated with HSCT in CR1. Conclusion: Although the number is small, this data suggests that 12p chromosomal changes in AML are significant adverse abnormalities, not different from complex cytogenetics, and treatment with HSCT does not change this dismal outcome. This also suggests that for patients with 12p abnormalities, alternative therapeutic approaches should be considered. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Long-term outcome after allogeneic stem cell transplantation in multiple myeloma

2021 ◽  
Author(s):  
Sini Luoma ◽  
Raija Silvennoinen ◽  
Auvo Rauhala ◽  
Riitta Niittyvuopio ◽  
Eeva Martelin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
Long Term Outcome ◽  
Significant Difference ◽  
Relapse Group

AbstractThe role of allogeneic hematopoietic stem cell transplantation (allo-SCT) in multiple myeloma is controversial. We analyzed the results of 205 patients transplanted in one center during 2000–2017. Transplantation was performed on 75 patients without a previous autologous SCT (upfront-allo), on 74 as tandem transplant (auto-allo), and on 56 patients after relapse. Median overall survival (OS) was 9.9 years for upfront-allo, 11.2 years for auto-allo, and 3.9 years for the relapse group (p = 0.015). Progression-free survival (PFS) was 2.4, 2.4, and 0.9 years, respectively (p < 0.001). Non-relapse mortality at 5 years was 8% overall, with no significant difference between the groups. Post-relapse survival was 4.1 years for upfront-allo and auto-allo, and 2.6 years for the relapse group (p = 0.066). Survival of high-risk patients was reduced. In multivariate analysis, the auto-allo group had improved OS and chronic graft-versus-host disease was advantageous in terms of PFS, OS, and relapse incidence. Late relapses occurred in all groups. Allo-SCT resulted in long-term survival in a small subgroup of patients. Our results indicate that auto-allo-SCT is feasible and could be considered for younger patients in the upfront setting.

Haploidentical Hematopoietic Stem Cell Transplantation without In Vitro T Cell Depletion for Treatment of Hematological Malignancies in Children.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5069-5069
Author(s):  
Daihong Liu ◽  
Xiao Jun Huang ◽  
Kaiyan Liu ◽  
Lanping Xu ◽  
Huan Chen ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Cumulative Incidence ◽  
Risk Group ◽  
T Cell Depletion ◽  
Hematopoietic Stem

Abstract Objective: To evaluate the efficacy and safety of haploidentical hematopoietic stem cell transplantation (HCT) for children with donors from family members. Patients and methods: Forty-two children under fourteen years old with hematologic malignancies underwent haploidentical HCT. The outcome was analyzed. Results: Four (9.5%) of the forty-two patients/donor pairs mismatched in one HLA locus, fifteen (35.7%) pairs in two loci and twenty three (54.8%) in three loci. They were followed up for a median of 612 (40–1779) days. All patients achieved stable engraftment. The cumulative incidence of acute graft-versus-host disease (GVHD) grade 2–4 was 57.2%, and that of grade 3–4 was 13.8%. The cumulative incidence of total and extensive chronic GVHD was 56.7% and 29.5%, respectively. The probability of leukemia-free survival was 65.1% in standard-risk group and 49.6% in high-risk group. Fourteen patients died, four from infection, six from relapse of leukemia, two from heart failure, one from severe acute GVHD, and one from lymphoproliferative disorders. The probability of relapse was 13.8% at 1 year and 27.9% at 2 year after transplantation. Conclusion: The results in this study encourage extending the haploidentical HCT without T-cell depletion to children with an indication for transplantation.

Long-Term Clinical Outcome of Children with Acquired Aplastic Anemia in Brazil.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4216-4216
Author(s):  
Marlene Pereira Garanito ◽  
Vicente Odone Filho ◽  
Marcela Vieira dos Santos ◽  
Elvira Velloso ◽  
Frederico L. Dulley ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Aplastic Anemia ◽  
Immunosuppressive Therapy ◽  
Cell Transplantation ◽  
Survival Probability ◽  
Conflicts Of Interest ◽  
Time History ◽  
Hematopoietic Stem ◽  
Significant Difference

Abstract Abstract 4216 Introdution/ Backgound Acquired Aplastic Anemia (AAA) is a rare hematologic disorder characterized by pancytopenia and hypocelular bone marrow. The pathophysiology is immune mediated in most cases. Environmental exposures to drugs, viruses and toxins, are thought to trigger the aberrant immune response in some patients. However, 50 to 74 percent of cases are classified as idiopathic. The highest frequency occurs in young population (15 to 25 years) with a second peak at age of 65 to 69 years. Immunosuppressive therapy is the best treatment in children with AAA who do not have a suitable donor for allogeneic stem cell transplantation. Materials and methods We reviewed the medical records of patients diagnosed with severe (SAA) and very severe acquired aplastic anemia (vSAA) at the Department of Pediatrics, Instituto da Criança – Hospital das Clínicas, University of Sào Paulo, Brazil from December, 1992 to December, 2007. We analyzed the clinical characteristics of the patients at diagnosis and the response to immunosuppressive therapy (IST) and hematopoietic stem cell transplantation (HSCT). Results In this study, 47 patients (27 boys and 20 girls), younger than 16 years, were diagnosed with vSAA (n= 21) or SAA (n=26). The median age was 7,71 years, ranging from 0.5 to 16 years and the average time history (beginning of signs and symptoms related to the disease and diagnosis) of the disease was 4,82 months, ranging from 0,25 to 48 months. Of the 47 patients, 45 had idiopathic AAA and 2 had hepatitis-associated. The median follow-up was 6,91 years for the patients treated with IST and 3,10 years for the patients who underwent to HSCT. One patient died before any treatment. For the eight patients who underwent to allogenic HLA-matched HSCT the 5-years-survival probability was 50%. For the 38 patients treated with IST, ten of them received cyclosporine and a short course of corticosteroids (CsA/CE) and 28 received antithymocyte globulin plus cyclosporine (ATG/CSA). The 5 years survival probability was 40% and 55%, respectively (p:0,0054). According to the severity of AAA, we did not show a significant difference in survival (p:0,32). Eight patients received second treatment after 1 year and 6 months (6 ATG from different species and CsA, 1 CsA and 1 thalidomide) and the probably of survival at 5 years was 60%. Among the 18 patients who responded to IST, four relapsed (22%). Two patients developed acute myeloid leukemia at 5 and 12 years after diagnosis. Conclusion Our results both for patients undergoing HSCT, as well as patients undergoing IST are lower in comparison to other hematological centers. Probably, this discrepancy is related to the prolonged time of disease when patients are admitted to our service. Unfortunately, the difficulty of access to specialized centers for diagnosis and early treatment in our country is a reality and this fact contributes to the delay to the beginning of treatment. Disclosures: No relevant conflicts of interest to declare.

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