Outcome of Allogeneic Hematopoietic Stem-Cell Transplantation for Acute Myeloid Leukemia (AML) with 11q23 (MLL) Rearrangement (MLL-r AML). A Retrospective Analysis From the Acute Leukemia Working Party of EBMT

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 498-498
Author(s):  
Arnaud Pigneux ◽  
Myriam Labopin ◽  
Johann Maertens ◽  
Ulrike Bacher ◽  
Gérard Socié ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Good Prognosis ◽  
Hematopoietic Stem ◽  
Long Term Outcome ◽  
The Impact ◽  
Acute Myeloid

Abstract Abstract 498 Acute myeloid leukemia (AML) with 11q23 (MLL) rearrangement (MLL-r AML) belongs to the intermediate or high risk cytogenetic classification. It prognosis is known to depend on the translocation partner. Data from multicenter studies suggest that most patients with t(11q23) achieve complete remission after induction chemotherapy. However, the impact of different t(11q23) on long-term outcome is less clear, with overall survival (OS) rates at 5 years ranging from 0% to 45%. A more favourable outcome has been reported in patients receiving an alloHSCT in an early phase. To investigate the potential role of alloHSCT for the management of t(11q23) AML we analyzed the outcome of the cases reported to the ALWP between 2000 and 2010 (median year of transplant: 2007). Overall, we identified 172 patients (median age: 41, 18–70; 43% male) allografted. The following rearrangements were identified: t(9;11) in 82 patients, t(11;19) in 20, t(6;11) in 21, t(10;11) in 17, t(4;11) in 5, t(11;17) in 5 and others in 22. Most transplants were performed in complete response (CR1=148, 86%; CR2=21, 12%, CR3=3, 2%). Donor was an HLA-identical sibling in 84 transplants (49%), and an unrelated in 88 (51%). Conditioning regimen consisted of a myeloablative regimen in most patients (n=113, 65%), and source of stem-cells was peripheral blood in 110 (64%), bone marrow in 49 (28%), and cord blood in 13 (8%). One hundred sixty-six patients engrafted and 57 presented an acute GVHD ≥ 2. After a median follow-up of 24 months (2–123), 2-year overall survival (OS) was 56 ± 4%, 2-year leukemia-free survival (LFS) was 52 ± 4%, CI of relapse incidence (RI) was 35±3%, non-relapse mortality (NRM) was 16±4% and the rate of chronic GVHD was 47±4%. The outcome was significantly different (p<10−4) according to the rearrangement with a 2-year LFS for patients with t(9;11) of 61±6%, t(11;19) of 65±11%, t(6;11) of 12±10%, t(10;11) of 34±12%. LFS was improved by CR status with a 2-y LFS for CR1 patients of 56 ± 5% and only 23 ± 9% for patients in more advanced disease. We subsequently restricted our analysis on the population of 148 patients in first CR in which the 2-year LFS was for patients with t(9;11) of 64±6%, t(11;19) of 68±12%, t(6;11) of 16±10%, t(10;11) of 40±13%, the 2-year RI was for patients with t(9;11) of 23±5%, t(11;19) of 26±11%, t(6;11) of 55±15%, t(10;11) of 36±14%, the 2-year NRM was for patients with t(9;11) of 24±13%, t(11;19) of 6±5%, t(6;11) of 29±13%, t(10;11) of 24±13%. Multivariate analysis on LFS identified as poor prognostic factors: the presence of a t(6;11)(p<0.0001) or t(10,11) (p = 0.034) and an interval from diagnosis to CR1 greater than 43 days (p=0.008). This preliminary study confirms the known good prognosis of t(9;11) and poor outcome of t(6;11), while it highlights the good prognosis of t(11;19) AML patients submitted to alloHSCT in CR1, suggesting that this procedure might overcome the adverse prognosis associated to this entity. Disclosures: No relevant conflicts of interest to declare.

Durable Remissions of Myelodysplastic Syndrome and Acute Myeloid Leukemia After Reduced-Intensity Allografting

2003 ◽  
Vol 21 (16) ◽  
pp. 3060-3065 ◽  
Author(s):  
D.C. Taussig ◽  
A.J. Davies ◽  
J.D. Cavenagh ◽  
H. Oakervee ◽  
D. Syndercombe-Court ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Myelodysplastic Syndrome ◽  
Myeloid Leukemia ◽  
Chronic Gvhd ◽  
Survival Rates ◽  
Conditioning Regimen ◽  
Hematopoietic Stem ◽  
Reduced Intensity ◽  
Acute Myeloid

Purpose: To evaluate the use of reduced-intensity (RI) conditioning with allogeneic hematopoietic stem cell transplantation (HSCT) from HLA-identical family donors in patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Patients and Methods: Sixteen patients (median age, 54 years; range, 37 to 66 years) underwent RI-HSCT using a conditioning regimen of fludarabine 25 mg/m2 daily for 5 days and either cyclophosphamide 1 g/m2 daily for 2 days (14 patients) or melphalan 140 mg/m2 for 1 day (two patients). The median number of CD34+ cells and CD3+ cells infused per kilogram of recipient weight was 4.5 × 106 (range, 1.8 to 7.3 × 106 cells) and 2.9 × 108 (range, 0.1 to 9.6 × 108 cells), respectively. Results: There was no transplant-related mortality (TRM) within 100 days of HSCT. Grade 1 to 2 acute graft-versus-host disease (GVHD) occurred in three patients, but neither grade 3 nor grade 4 disease was observed. Chronic GVHD occurred in 10 patients. One patient had cytomegalovirus (CMV) reactivation but did not develop CMV disease. With a median follow-up of 26 months (range, 15 to 45 months), 11 patients are alive (nine in continuous complete remission and one in complete remission after a second transplantation), and five have died (four from disease progression and one from bone-marrow aplasia induced by cyclosporine withdrawal). The 2-year actuarial overall and event-free survival rates were 69% (95% confidence interval [CI], 40% to 86%) and 56% (95% CI, 30% to 68%), respectively. Conclusion: This strategy of RI-HSCT resulted in reliable engraftment with low incidence of acute GVHD and TRM. Durable remissions were observed in patients with MDS and AML consistent with a graft-versus-leukemia effect.

AML1/RUNX1 mutations in 470 adult patients with de novo acute myeloid leukemia: prognostic implication and interaction with other gene alterations

Blood ◽  
2009 ◽  
Vol 114 (26) ◽  
pp. 5352-5361 ◽  
Author(s):  
Jih-Luh Tang ◽  
Hsin-An Hou ◽  
Chien-Yuan Chen ◽  
Chieh-Yu Liu ◽  
Wen-Chien Chou ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Remission Rate ◽  
Adult Patients ◽  
Poor Prognostic Factor ◽  
The Impact ◽  
Runx1 Mutation ◽  
Acute Myeloid

AbstractSomatic mutation of the AML1/RUNX1(RUNX1) gene is seen in acute myeloid leukemia (AML) M0 subtype and in AML transformed from myelodysplastic syndrome, but the impact of this gene mutation on survival in AML patients remains unclear. In this study, we sought to determine the clinical implications of RUNX1 mutations in 470 adult patients with de novo non-M3 AML. Sixty-three distinct RUNX1 mutations were identified in 62 persons (13.2%); 32 were in N-terminal and 31, C-terminal. The RUNX1 mutation was closely associated with male sex, older age, lower lactic dehydrogenase value, French-American-British M0/M1 subtypes, and expression of HLA-DR and CD34, but inversely correlated with CD33, CD15, CD19, and CD56 expression. Furthermore, the mutation was positively associated with MLL/PTD but negatively associated with CEBPA and NPM1 mutations. AML patients with RUNX1 mutations had a significantly lower complete remission rate and shorter disease-free and overall survival than those without the mutation. Multivariate analysis demonstrated that RUNX1 mutation was an independent poor prognostic factor for overall survival. Sequential analysis in 133 patients revealed that none acquired novel RUNX1 mutations during clinical courses. Our findings provide evidence that RUNX1 mutations are associated with distinct biologic and clinical characteristics and poor prognosis in patients with de novo AML.

scholarly journals Oral mucositis in patients with acute myeloid leukemia treated with allogeneic hematopoietic stem cell transplantation in relation to the conditioning used prior to transplantation

2021 ◽  
Author(s):  
Aleksandra Wysocka-Słowik ◽  
Lidia Gil ◽  
Zuzanna Ślebioda ◽  
Agnieszka Kręgielczak ◽  
Barbara Dorocka-Bobkowska
Keyword(s):  
Acute Myeloid Leukemia ◽  
Cell Transplantation ◽  
Oral Mucositis ◽  
Myeloid Leukemia ◽  
Hematopoietic Cell Transplantation ◽  
Conditioning Regimen ◽  
World Health ◽  
Post Transplantation ◽  
Hematopoietic Stem ◽  
Acute Myeloid

AbstractThis study was designed to investigate the frequency and severity of oral mucositis in patients with acute myeloid leukemia after allogeneic hematopoietic cell transplantation, in relation to the type of conditioning used. Eighty patients diagnosed with acute myeloid leukemia were assigned to two groups based on the conditioning regimen used before transplantation. The intensity of oral inflammatory lesions induced by chemotherapy (oral mucositis) was evaluated according to a 5-point scale recommended by World Health Organization. Oral mucosa was investigated in all patients before the transplantation and during two subsequent stages of the post-transplantation procedure in relation to the conditioning regimen used. Mucositis in the oral cavity was observed in the majority of patients (66%) in the first week after transplantation, whereas the largest percentage of patients suffering oral lesions (74%) occurred in the second week after transplantation. A significantly higher percentage of patients with mucositis was observed in the group which underwent myeloablation therapy (74% of MAC and 50% of RIC patients in the first week; 83% of MAC and 53% of RIC patients in the second examination).The severity of mucositis after transplantation was higher in the MAC patients compared to the RIC patients. The highest mean value of the mucositis index was recorded in the second week in the MAC group (1.59). In AML sufferers receiving allo-HSCT, oral mucositis is a significant complication of the transplantation. This condition is more frequent and more severe in patients after treatment with myeloablation therapy.

scholarly journals Low expression of MN1 associates with better treatment response in older patients with de novo cytogenetically normal acute myeloid leukemia

Blood ◽  
2011 ◽  
Vol 118 (15) ◽  
pp. 4188-4198 ◽  
Author(s):  
Sebastian Schwind ◽  
Guido Marcucci ◽  
Jessica Kohlschmidt ◽  
Michael D. Radmacher ◽  
Krzysztof Mrózek ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Hox Genes ◽  
De Novo ◽  
Prognostic Significance ◽  
The Impact ◽  
Favorable Group ◽  
Acute Myeloid

AbstractLow MN1 expression bestows favorable prognosis in younger adults with cytogenetically normal acute myeloid leukemia (CN-AML), but its prognostic significance in older patients is unknown. We analyzed pretherapy MN1 expression in 140 older (≥ 60 years) de novo CN-AML patients treated on cytarabine/daunorubicin-based protocols. Low MN1 expressers had higher complete remission (CR) rates (P = .001), and longer overall survival (P = .03) and event-free survival (EFS; P = .004). In multivariable models, low MN1 expression was associated with better CR rates and EFS. The impact of MN1 expression on overall survival and EFS was predominantly in patients 70 years of age or older, with low MN1 expressers with mutated NPM1 having the best outcome. The impact of MN1 expression was also observed in the Intermediate-I, but not the Favorable group of the European LeukemiaNet classification, where low MN1 expressers had CR rates and EFS similar to those of Favorable group patients. MN1 expresser-status-associated gene- and microRNA-expression signatures revealed underexpression of drug resistance and adverse outcome predictors, and overexpression of HOX genes and HOX-gene–embedded microRNAs in low MN1 expressers. We conclude that low MN1 expression confers better prognosis in older CN-AML patients and may refine the European LeukemiaNet classification. Biologic features associated with MN1 expression may help identify new treatment targets.

scholarly journals GATA2 Related Conditions and Predisposition to Pediatric Myelodysplastic Syndromes

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2962
Author(s):  
Antonella Bruzzese ◽  
Davide Leardini ◽  
Riccardo Masetti ◽  
Luisa Strocchio ◽  
Katia Girardi ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndromes ◽  
Myeloid Leukemia ◽  
Nk Cell ◽  
Bone Marrow Failure ◽  
Conditioning Regimen ◽  
Mycobacterial Infection ◽  
Optimal Time ◽  
Hematopoietic Stem ◽  
Acute Myeloid

Myelodysplastic syndromes (MDS) are hematopoietic disorders rare in childhood, often occurring in patients with inherited bone marrow failure syndromes or germinal predisposition syndromes. Among the latter, one of the most frequent involves the gene GATA binding protein 2 (GATA2), coding for a transcriptional regulator of hematopoiesis. The genetic lesion as well as the clinical phenotype are extremely variable; many patients present hematological malignancies, especially MDS with the possibility to evolve into acute myeloid leukemia. Variable immune dysfunction, especially resulting in B- and NK-cell lymphopenia, lead to severe infections, including generalized warts and mycobacterial infection. Defects of alveolar macrophages lead to pulmonary alveolar proteinosis through inadequate clearance of surfactant proteins. Currently, there are no clear guidelines for the monitoring and treatment of patients with GATA2 mutations. In patients with MDS, the only curative treatment is allogeneic hematopoietic stem cell transplantation (HSCT) that restores normal hematopoiesis preventing the progression to acute myeloid leukemia and clears long-standing infections. However, to date, the donor type, conditioning regimen, and the optimal time to proceed to HSCT, as well as the level of chimerism needed to reverse the phenotype, remain unclear highlighting the need for consensus guidelines.

Mitoxantrone, Etoposide, and Intermediate-Dose Cytarabine in the Treatment of Refractory/Relapsed Acute Myeloid Leukemia : Single-Center Experience

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4007-4007
Author(s):  
Hwa Jung Sung ◽  
Eui Bae Kim ◽  
Se Ryeon Lee ◽  
Hee Yun Seo ◽  
Kyong Hwa Park ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Prognostic Significance ◽  
Salvage Chemotherapy ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Relapsed Acute Myeloid Leukemia ◽  
Acute Myeloid

Abstract Background: The results of salvage chemotherapy for patient with refractory or relapsed acute myeloid leukemia(AML) have been generally disappointing with low response rates and occasional long-term survivors in most studies. Since therapeutic failure seems to be inevitable in the great majority of these patients, development of more effective salvage therapy is warranted. Recent approaches to the treatment of previously treated AML generally involved the use of cytarabine in intermediate or high-dose alone or in association with new intercalating agents, such as amsacrine, mitoxantrone or idarubicin, etoposide, or asparaginase. Methods: A single course of mitoxantrone 6 mg/m2 intravenous (IV) bolus, etoposide 80 mg/m2 IV for 1 hour, and cytarabine (Ara-C) 1g/m2 IV for 6 hours daily for 6 days (MEC), has been proposed as a salvage regimen. Between October 1998 and May 2005, thirty refractory/relapsed AML patients have been treated by MEC salvage chemotherapy. Twenty two patients were in relapse and eight patients were refractory after conventional induction chemotherapy including cytarabine and idarubicin or mitoxantrone. Two patient were in relapse after allogenous hematopoietic stem cell transplantation(SCT). Results: Complete remission(CR) was obtained in 12 of 30 patients(40%) and 3 of 30(10%) died during salvage treatment: 2 due to intracranial hemorrhage and 1 due to fungemia sepsis. After CR achievement, 5 patients received consolidation chemotherapy. Two patients with an HLA-identical sibling donor underwent allogeneic SCT, and one patient received autologous SCT. Severe myelosuppression was observed in all patients resulting in fever or documented infections in 90% of patients. Nonhematologic toxicity was minimal. At the time of analysis, 9 of 11 patients who achieved CR have relapsed. Median disease-free survival was 12 months. Median overall survival was 13.5 months. There were only two longterm remitters. Several clinicolaboratory and treatment-related variables were analyzed to determine their prognostic significance for CR achievement, duration of CR, overall survival. Conclusions: Our results suggest that MEC combination chemotherapy might induce CR in a patient with refractory or relapsed AML, although new agents or new therapeutic strategies should be required for long term remission.

Allogeneic Stem Cell Transplantation (allo-SCT) for Secondary Acute Myeloid Leukemia (AML) Following Breast Carcinoma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3305-3305
Author(s):  
Sameh Ayari ◽  
Mohamad Mohty ◽  
Karin Bilger ◽  
Gaelle Guillerm ◽  
Denis Guyotat ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Breast Carcinoma ◽  
Myeloid Leukemia ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Increased Risk ◽  
Acute Myeloid

Abstract Abstract 3305 Poster Board III-193 Patients with breast carcinoma who received Radio and/or chemotherapy, have an increased risk for developing therapy-related myelodysplastic syndromes/acute myeloid leukemia (1-5%). Such secondary AMLs have often poor prognosis when treated with conventional chemotherapy. This retrospective series assessed the outcome of 29 female patients who were reported to the Societe Francaise de Greffe de Moelle et de Therapie Cellulaire Registry, and who were treated with allo-SCT for secondary MDS/AML developing after initial therapy for breast cancer. The median age of patients at time of breast cancer treatment was 51 (range, 31-62) years. The median age at time of allo-SCT was 53 (range 31-63) years. Diagnosis included 21 AML and 8 MDS. Cytogenetics: four patients had CBF abnormalities, 10 had 11q23 abnormalities, 5 had an intermediate caryotype and 3 had unfavourable one. At time of allo-SCT, 21 patients were in complete remission (CR), while 8 had a refractory/relapsed disease. PBSCs were used as stem cell source in 18 patients, while 9 patients received classical bone marrow and one patient received an unrelated umbilical cord blood. Patients received a median of 5.2 ×10e6/Kg CD34+ cells. A matched related donor was used in 23 cases (82%) and an unrelated donor in 5 cases (18%). Conditioning regimen was myeloablative (Cy-TBI or Bu-Cy) in 7 cases (24%) and reduced-intensity in 22 cases (76%). Twenty four patients engrafted with a median time of 18 (range, 9-32) days for ANC>500/μL. Seven (24%) patients experienced grade 2-4 acute GVHD. Also, 7 patients (24%) experienced chronic GVHD (5 extensive and 2 limited). With a median follow-up of 24 (range, 3-129) months, 16 patients (55%) were still alive. Disease progression accounted for 6 deaths while transplant related causes (infection n=4, GVHD n=1, MOF n=1, cardiac failure n=1) occurred in 7 cases. The Kaplan-Meier estimates of overall and disease-free survival at 2 years were at 54 and 38% respectively. These results highlight the poor outcome of secondary leukemia occurring after therapy for breast cancer, even with the use of allo-SCT. Innovative maintenance approaches such as early use of hypomethylating or immunomodulatory agents after allo-SCT aiming to decrease the relapse are warranted. Disclosures No relevant conflicts of interest to declare.

Characterization of Extramedullary Acute Myeloid Leukemia – Results of the AML96 Trial

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2154-2154
Author(s):  
Friedrich Stölzel ◽  
Christoph Röllig ◽  
Michael Kramer ◽  
Brigitte Mohr ◽  
Uta Oelschlägel ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
The Body ◽  
Hematopoietic Stem ◽  
Npm1 Mutation ◽  
Mutation Status ◽  
The Impact ◽  
Acute Myeloid

Abstract Abstract 2154 Background: Myeloid Sarcoma (MS) is defined as an extramedullary mass composed of myeloid blasts occurring at an anatomical site other than the bone marrow. Furthermore, the term extramedullary manifestation (EM) is applied if it accompanies overt acute myeloid leukemia (AML) and represents non-effacing tissue infiltration. EM is reported to correspond often to the skin but can affect almost every site of the body. The prognosis of MS or EM has been discussed controversially in the past. EM at diagnosis of AML is generally thought to be a rare event. However, data defining the prevalence of EM at diagnosis of AML and its prognostic value are missing. The aim of this analysis was to provide data for estimating the prevalence of EM at diagnosis of AML and to determine its relevance by including clinical and laboratory data from patients being treated in the prospective AML96 trial of the Study Alliance Leukemia (SAL) study group. Patients and Methods: A total of 326 patients with AML (age 17 – 83 years) and EM were treated within the AML96 trial with a median follow up of 8.8 years (95% CI, 8.4 to 9.3 years). All patients received double induction chemotherapy. Consolidation therapy contained high-dose cytosine arabinoside and for patients ≤ 60 years of age the option of autologous or allogeneic hematopoietic stem cell transplantation (HSCT). Logistic regression analyses were used to identify prognostic variables for CR rates. The method of Kaplan-Meier was used to estimate OS and EFS. Confidence interval (CI) estimation for the survival curves was based on the cumulative hazard function using the Greenwood's formula for the SE estimation. Survival distributions were compared using the log rank test. Results: 17% of the AML patients entered into the AML96 trial were diagnosed with EM. In 313 of the 326 patients (96%) EM was evident at diagnosis. The majority of patients with EM were diagnosed with de novo AML (84%, n=273), whereas gingival infiltration (51%, n=166) displayed the main EM of AML with CNS involvement being less common (4%, n=14). The majority of patients had a cytogenetic intermediate risk profile (71%, n=221) with a total of 172 patients (56%) harboring a normal karyotype. Patients with EM had a statistically significant lower median CD34-positivity of bone marrow blasts, higher percentage of FAB subtypes M4 and M5, higher WBC counts and LDH at diagnosis and higher percentage of NPM1 mutations compared to those patients without EM (all p<.001). When comparing achievement of CR between patients with EM to patients without EM, no statistical difference between these two groups was observed. Analysis according to the NPM1/FLT3-ITD mutation status revealed highest 5-year-OS (37%, 95% CI: .24 - .508) and 5-year-EFS (36%, 95% CI: .224 - .448) in the NPM1-mut/FLT3-wt group and lowest 5-year-OS (12%, 95% CI: 0 - .261) and 5-year-EFS (4%, 95% CI: 0 - .124) in the NPM1-wt/FLT3-ITD group, p=.007 and p=.001, respectively. Of the 49 relapsed patients with EM who had a NPM1-mutation at diagnosis 48 deceased despite of intensified relapse therapies. Conclusions: This analysis represents the largest study so far investigating the impact of EM AML. Patients with EM AML have distinct differences from AML patients without EM regarding their clinical and molecular characteristics at diagnosis. However these differences do not translate into differences in response to induction chemotherapy. Compared to patients without EM, survival analysis revealed differences according to the NPM1/FLT3-ITD mutation status which is also described for patients without EM AML. However, the prognosis for patients with EM who harbor a mutated NPM1 the prognosis at relapse seems to be dismal. Disclosures: No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document