Characteristics and outcomes of patients diagnosed with DNMT3A mutated acute myeloblastic leukemia.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19018-e19018
Author(s):  
Daniel Rivera ◽  
Hagop M. Kantarjian ◽  
Tapan M. Kadia ◽  
Naval Guastad Daver ◽  
Courtney Denton Dinardo ◽  
...  
Keyword(s):  
Tp53 Mutation ◽  
De Novo ◽  
Negative Impact ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Complete Response ◽  
P Value ◽  
Prognostic Impact ◽  
Intensive Chemotherapy ◽  
Secondary Aml

e19018 Background: Advances in molecular profiling have identified recurring gene mutations in acute myeloid leukemia (AML) that have independent prognostic significance with several being targets for the development of new small molecule inhibitors. DNMT3A mutations have been reported in up to 34% of patients with AML. Mutations of this gene are associated with silencing of tumor suppressor genes, thereby leading to leukemogenesis. Several prior reports have suggested an association with worse outcomes. Methods: We retrospectively reviewed records of 258 patients with ND AML with DNMT3A mutations who presented to our institution from 2002 to 2020. We analyzed their clinical and laboratory characteristics. We estimated their overall survival (OS) and disease-free survival (DFS) through the Kaplan-Meier method. P-value was 2-tailed, ≤ 0.05 was considered statistically significant with a confidence interval of 95%. Univariate and multivariate analyses were also applied. Results: Our cohort had a median age of 66 years, 56% were female. The majority of the patients (77%) had de novo AML and the M0 FAB subtype was predominantly observed in 70%. Diploid karyotype was detected in 60% while complex karyotype in 14% of patients. DNMT3A was most frequently mutated at codon 882 (64%). NPM1 was the most frequent concomitant mutation followed by FLT3-ITD and IDH2. Age > 65 years (p = 0.001) and presence of concomitant TP53 mutation (p < 0.001) were associated with worse survival and concomitant NPM1 was associated with a 40% reduction of death, p = 0.003. Secondary AML and concurrent TP53 mutation were associated with a higher risk of relapse, (p < 0.001 for both). Intensive chemotherapy (ICT) was administered to 82 patients of which 68 achieved a complete response or CR with incomplete count recovery (CRi). Nineteen patients were treated with Cladribine plus low dose Ara-C (Clad-LDAC) and CR or CRi was achieved in 16 patients. Eleven treated with Clad-LDAC-Ven and all achieved CR/CRi. Hypomethylating agents (HMA) were given to 22 patients of which 10 achieved CR/CRi. Twenty-five received HMA-Ven, of these, CR/CRi was achieved in 20 patients (p = 0.02). There was an 80% and 90% reduction of death with ICT, p < 0.001 and Clad-LDAC-Ven, p = 0.04 respectively. Moreover, the risk for relapse was reduced by 70% and 90% with ICT and Clad-LDAC-Ven respectively. Ninety-seven patients were treated with immunotherapy, FLT3 inhibitors, and IDH inhibitors, which were not included in this analysis. Conclusions: DNMT3A mutations have an independent prognostic impact in patients diagnosed with AML. Among these patients, older age, secondary AML, a concomitant mutation in TP53 showed a significant negative impact in terms of OS and DFS. Concomitant mutations in NPM1 and IDH2 were associated with better outcomes. Treatment with intensive chemotherapy or clad-LDAC-Ven was associated with the highest response rates.

scholarly journals Prognostic impact of cytogenetic abnormalities in patients with de novo acute nonlymphocytic leukemia

Blood ◽  
1989 ◽  
Vol 73 (1) ◽  
pp. 263-270 ◽  
Author(s):  
CA Schiffer ◽  
EJ Lee ◽  
T Tomiyasu ◽  
PH Wiernik ◽  
JR Testa
Keyword(s):  
De Novo ◽  
Disease Free Survival ◽  
Complete Response ◽  
Prognostic Impact ◽  
Acute Nonlymphocytic Leukemia ◽  
Trisomy 8 ◽  
Cytogenetic Changes ◽  
Cytogenetic Analyses ◽  
Resolution Banding

Abstract Detailed cytogenetic analyses were performed on specimens from 198 patients with de novo acute nonlymphocytic leukemia (ANLL), including high-resolution banding studies in 79 patients. One hundred ninety-two patients received induction therapy with daunorubicin and cytosine arabinoside (Ara-C) with an overall complete response rate (CR) of 63%. Responding patients received repetitive cycles of Ara-C-based intensification therapy. Clonal abnormalities were detected in 69% of the patients with specimens adequate for cytogenetic analysis. Certain cytogenetic changes were closely associated with French-American- British (FAB) morphology, age, and outcome: t(8;21) (closely associated with FAB M2), t(15;17) (associated with FAB M3), and abn 16q22 (associated with FAB M4EOS) tended to occur in younger patients and were associated with favorable outcomes in terms of both CR rate and long-term disease-free survival. In contrast, 19% of patients who had - 5/5q- and or -7/7q- and seven patients with trisomy 8 were older, had a poor prognosis, and usually failed to achieve remission (CR) because of chemotherapy-resistant leukemia. The adverse effect on CR rate and duration in this group of patients was independent of age, and there was no association with particular morphologic subtypes. These data suggest that cytogenetic findings should influence future therapeutic choices. In particular, patients with abnormalities associated with poor responses may be considered for investigational approaches and may also provide insights into mechanisms of drug resistance.

scholarly journals Prognostic impact of acellular mucin pools towards the patients with locally advanced rectal cancer achieving pathological complete response after preoperative chemoradiotherapy

2020 ◽  
Vol 13 ◽  
pp. 175628482091125
Author(s):  
Lin Zhang ◽  
Huajie Guan ◽  
Qiuyun Luo ◽  
Lifang Yuan ◽  
Yulan Mao ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Pathological Complete Response ◽  
Locally Advanced ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Preoperative Chemoradiotherapy ◽  
Locally Advanced Rectal Cancer ◽  
Prognostic Impact

Background: To date, the prognostic significance of acellular mucin pools in tumors from patients with locally advanced rectal cancer (LARC) undergoing preoperative chemoradiotherapy (CRT) and subsequently obtaining pathological complete response (pCR) has not been well determined. Our current study aimed to explore the prognostic impact on these patients of acellular mucin pools. Methods: We collected clinical data from 117 consecutive LARC patients who achieved pCR after preoperative CRT and then underwent radical resection. Two groups of patients were generated, according to the presence or absence of acellular mucin pools. The 5-year disease-free survival (DFS) and overall survival (OS) rates were compared between the two groups of patients. Results: A total of 27 (23.1%) patients presented with acellular mucin pools. At a median follow-up period of 64 months, patients with acellular mucin pool showed a 5-year DFS rate (96.3% versus 83.7%, p = 0.110) and 5-year OS rate (100% versus 87.5%, p = 0.054) statistically similar to those of patients without acellular mucin pools. In univariable and multivariable Cox regression analyses, the presence of acellular mucin pools was not determined as an independent risk factor for DFS [hazard ratio (HR): 0.222; 95% confidence interval (CI): 0.029–1.864; p = 0.145] or OS (HR: 0.033; 95% CI: 0.000–9.620; p = 0.238). Conclusions: Acellular mucin pools had no significant prognostic impact on LARC patients showing pCR after preoperative CRT.

scholarly journals Prognostic impact of cytogenetic abnormalities in patients with de novo acute nonlymphocytic leukemia

Blood ◽  
1989 ◽  
Vol 73 (1) ◽  
pp. 263-270 ◽  
Author(s):  
CA Schiffer ◽  
EJ Lee ◽  
T Tomiyasu ◽  
PH Wiernik ◽  
JR Testa
Keyword(s):  
De Novo ◽  
Disease Free Survival ◽  
Complete Response ◽  
Prognostic Impact ◽  
Acute Nonlymphocytic Leukemia ◽  
Trisomy 8 ◽  
Cytogenetic Changes ◽  
Cytogenetic Analyses ◽  
Resolution Banding

Detailed cytogenetic analyses were performed on specimens from 198 patients with de novo acute nonlymphocytic leukemia (ANLL), including high-resolution banding studies in 79 patients. One hundred ninety-two patients received induction therapy with daunorubicin and cytosine arabinoside (Ara-C) with an overall complete response rate (CR) of 63%. Responding patients received repetitive cycles of Ara-C-based intensification therapy. Clonal abnormalities were detected in 69% of the patients with specimens adequate for cytogenetic analysis. Certain cytogenetic changes were closely associated with French-American- British (FAB) morphology, age, and outcome: t(8;21) (closely associated with FAB M2), t(15;17) (associated with FAB M3), and abn 16q22 (associated with FAB M4EOS) tended to occur in younger patients and were associated with favorable outcomes in terms of both CR rate and long-term disease-free survival. In contrast, 19% of patients who had - 5/5q- and or -7/7q- and seven patients with trisomy 8 were older, had a poor prognosis, and usually failed to achieve remission (CR) because of chemotherapy-resistant leukemia. The adverse effect on CR rate and duration in this group of patients was independent of age, and there was no association with particular morphologic subtypes. These data suggest that cytogenetic findings should influence future therapeutic choices. In particular, patients with abnormalities associated with poor responses may be considered for investigational approaches and may also provide insights into mechanisms of drug resistance.

Extramedullary Infiltrates of AML: Biological and Clinical Features in a Single Centre Experience.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4513-4513
Author(s):  
Paola Carluccio ◽  
Domenico Pastore ◽  
Arcangelo Liso ◽  
Francesco Albano ◽  
Anna Mestice ◽  
...  
Keyword(s):  
Soft Tissue ◽  
De Novo ◽  
Risk Group ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Antigen Expression ◽  
Complete Response ◽  
The Body ◽  
Rate Analysis ◽  
De Novo Aml

Abstract Extramedullary infiltration (EMI) of malignant myeloid precursor cells in acute myeloid leukemia (AML) may occasionally be a presenting clinical symptom at onset and may develop at any site in the body but most commonly in the gum, skin, central nervous system (CNS) and soft tissue. There is controversy about the prognostic significance of extramedullary disease in AML. The present study examines the incidence, the biological features and prognostic significance of EMI at diagnosis in adult patients with AML. From January 1997 to December 2004, 213 untreated patients with de novo AML were studied. According to Grimwade et al, 14 patients were in the favorable-risk group, 159 in the intermediate-risk group, 25 in the poor risk group and in 15 the karyotype was not available. All patients had been treated with induction therapy according to the GIMEMA protocols including cytarabine, etoposide and idarubicin (15 pts), or mitoxantrone (15 pts) or daunorubicin (183 pts). Of 213 cases with de novo AML, 29 (14%) had EMI at diagnosis. Ten patients (34.8%) had skin infiltrates, 12 (41.4%) had gum hypertrophy, 5 (17.2%) had CNS involvement and 2 (6.9%) had soft tissue infiltration. No significant differences in terms of sex, age median Hb level and platelets count were found between patients with EMI and patients without EMI. The patients with EMI had higher median WBC counts (27 × 109/L) than patients without EMI (8.5 × 109/L) (p=0.05). The patients with EMI had a higher incidence of the M4/M5 FAB subtype (62%) than patients without EMI (27.4%) (p=0.005). Cytogenetic analysis was performed in patients with and without EMI; none of the abnormal cytogenetic findings was associated with EMI. We evaluated the relationship between the AML blasts surface antigen expression and EMI; the association between CD56/CD4 and CD56/CD14 was more significantly expressed in patients with EMI (35% and 29%, respectively) than without EMI (10.4% and 6.9%, respectively) (p=0.004, p=0.003). The overall CR rate was 65%; the CR rate was lower in patients with EMI (48.2%) than patients without EMI (76.1%) (p=0.001) and their disease free survival was also shorter (p=0.017); the median duration of CR was 10 and 25 months (range 2–96) in EMI and no EMI group, respectively. Our data show that a high WBC count, M4/M5 subtype, CD56/CD4 and CD56/CD14 expression are associated with extramedullary infiltrates of AML at diagnosis; the presence of EMI adversely affects the complete response rate to induction chemotherapy and the OS rate. Analysis of the clinical and biologic features in a larger series of adult AML patients is needed to evaluate the allocation of this subgroup in a different or more intensive treatment arm.

Prognostic Impact of the Amount of CD34+ CD38- CD123+ Cells at Diagnosis In Acute Myeloid Leukemia: a Study From the GOELAMS

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 951-951
Author(s):  
François Vergez ◽  
Alexa Green ◽  
Jérôme Tamburini ◽  
Nathalie Gallay ◽  
Murielle Roussel ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
De Novo ◽  
Conflicts Of Interest ◽  
Disease Free Survival ◽  
Complete Response ◽  
Leukemic Cells ◽  
Prognostic Impact ◽  
Npm1 Mutation ◽  
Number Of Patients ◽  
Wbc Count

Abstract Abstract 951 AML cells with CD34+CD38-CD123+ phenotype represent a subset enriched in leukemic stem cells. Moreover, this subpopulation has been described to be resistant to genotoxic agents as compared with leukemic bulk. However, the clinical impact of the amount of CD34+CD38-CD123+ remains poorly described. In this study we evaluated the prognostic impact of the amount of CD34+CD38-CD123+ cells detected at diagnosis in a series of AML patients treated by intensive chemotherapy according to trials from the French GOELAMS group. Quantification of blast cells with the CD34+CD38-CD123+ phenotype was achieved by flow cytometry in 111 patients less than 66 years old with de novo AML treated by 3+7-like chemotherapy. The characteristics of the patients are shown in table 1. Age, WBC count, NPM1 mutation and FLT3-ITD had no impact on achievement of complete response (CR) whereas, CD34+CD38-CD123+ (>15%) and unfavourable karyotype were significantly correlated with lack of CR. By logistic regression, CD34+CD38-CD123+ (>15%) retains significance for CR achievement with an OR of 0.3 (0.11-0.84) (p=0.02). For the 91 complete responders, age, WBC count, karyotype, NPM1 mutation had no impact on disease-free survival (DFS).Interestingly, patients with <1%, 1–15%, >15% CD34+CD38-CD123+ had a median DFS of 57.6 (SE 6.6), 11.2 (SE 7.5) and 9.2 (SE 13.4) months, respectively (p<0.0001, figure 1). FTL3-ITD was also significantly associated with a shorter DFS. In multivariate analysis, CD34+CD38-CD123+<1% was significantly associated with a longer DFS (p=0.00025). Age, %CD34+CD38-CD123+, karyotype, NPM mutation and FLT3-ITD significantly influenced overall survival (OS) whereas WBC count had no impact. Median OS was particularly impressive for patients with CD34+CD38-CD123+<1%. Indeed, median OS was 78.2 (SE 10.7), and 15.3 (SE 5.8) months for CD34+CD38-CD123+<1% vs others, respectively (p<0.0001, figure 1). Multivariate analysis for OS retains two significant factors: adverse karyotype (95%CI, 1.19–4.02, p=0.012) and CD34+CD38-CD123+<1% (95%CI, 0.12–0.52, p=0.00018). Moreover, although the number of patients was low in favourable karyotype (CBF), CD34+CD38-CD123+<1% had a major impact on both DFS, median 57.6 vs 10.2 months for >1% (HR, 0.19, 0.06–0.59, p=0.0038) and OS, median not reached vs 18.5 months (p=0.0025). This study emphasizes the prognosis impact of the CD34+CD38-CD123+ cell burden in AML patients, which is predictive for shorter OS and DFS when representing more than 1% of the leukemic cells, regardless of the usual prognosis categories. We provide here a new prognosis marker that may be easily translated to the clinical practice in AML although it remains to be validated on a large prospective cohort of patients. Moreover, new therapies targeting this subpopulation could help to improve outcome in AML patients.TableCharacteristics of patients.All patients N=111CD34+CD38-CD123+< 1 % N=40CD34+CD38-CD123+ 1-15% N=20CD34+CD38-CD123+> 15% N=20Gender, M/F50/6219/2124/276/14Age, median48 (20–65)47 (20–65)51 (20–64)50 (21–65)WBC,median (G/L)33.2 (1–254)13.8 (1–237.7)41 (1.3–254)32.9 (2.3–193.2)Favourable caryotype231184Intermediate caryotype6924378Unfavourable caryotype19568NPM1 mutation28/957/3116/455/19FLT3-ITD33/1007/3421/475/19Complete Response91 (82%)36 (90%)42 (81.4%)13 (65%)Relapse53 (58.2%)13 (36.1%)30 (71.4%)10 (76.9%)Allogeneic-SCT33 (36.3%)11 (30.6%)15 (35.7%)7 (53.8%) Disclosures: No relevant conflicts of interest to declare.

scholarly journals The prognostic significance of pretreatment serum γ-glutamyltranspeptidase in primary liver cancer: a meta-analysis and systematic review

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Yang Ou ◽  
Junwei Huang ◽  
Liping Yang
Keyword(s):  
Liver Cancer ◽  
Primary Liver Cancer ◽  
Meta Analysis ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Prognostic Impact ◽  
Free Survival ◽  
Effect Measure ◽  
Pretreatment Serum ◽  
Disease Free

Aim: To assess the prognostic value of the pretreatment serum γ-glutamyltranspeptidase (GGT) level in patients with primary liver cancer (PLC). Methods: Relevant studies were systematically searched online on Web of Science, PubMed, and Embase databases published until 9 October 2018. The end points were overall survival (OS), recurrence-free survival (RFS), and disease-free survival (DFS). Meta-analysis was conducted using hazard ratio (HR), and its 95% confidence interval (CI) as effect measure. Results: A total of 33 eligible studies with 9238 patients with PLC were included in this meta-analysis. The synthesized analysis showed that that higher serum GGT level was significantly related to poorer OS (HR: 1.79, 95% CI: 1.66–1.93, P<0.01), RFS (HR: 1.60, 95% CI: 1.46–1.77, P<0.01), and DFS (HR: 1.52, 95% CI: 1.33–1.73, P<0.01) of patients with PLC. Subgroup analyses demonstrated that the negative prognostic impact of higher serum GGT level on OS and RFS was still of significance regardless of ethnicity, pathological type, sample size, cut-off value, first-line treatment, and analysis type. Conclusion: The pretreatment serum GGT might be a predictive factor of poor prognosis for PLC patients.

scholarly journals Distinct clinical and biological characteristics of acute myeloid leukemia with higher expression of long noncoding RNA KIAA0125

2020 ◽  
Author(s):  
Yu-Hung Wang ◽  
Chien-Chin Lin ◽  
Chia-Lang Hsu ◽  
Sheng-Yu Hung ◽  
Chi-Yuan Yao ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Noncoding Rna ◽  
De Novo ◽  
Remission Rate ◽  
Prognostic Significance ◽  
Multivariable Analysis ◽  
Disease Free Survival ◽  
Biological Characteristics ◽  
Acute Myeloid

AbstractExpression of long non-coding RNA KIAA0125 has been incorporated in various gene expression signatures for prognostic prediction in acute myeloid leukemia (AML) patients, yet its functions and clinical significance remain unclear. This study aimed to investigate the clinical and biological characteristics of AML bearing different levels of KIAA0125. We profiled KIAA0125 expression levels in bone marrow cells from 347 de novo AML patients and found higher KIAA0125 expression was closely associated with RUNX1 mutation, but inversely correlated with t(8;21) and t(15;17) karyotypes. Among the 227 patients who received standard chemotherapy, those with higher KIAA0125 expression had a lower complete remission rate, shorter overall survival (OS) and disease-free survival (DFS) than those with lower expression. The prognostic significance was validated in both TCGA and GSE12417 cohorts. Subgroup analyses showed that higher KIAA0125 expression also predicted shorter DFS and OS in patients with normal karyotype or non-M3 AML. In multivariable analysis, higher KIAA0125 expression remained an adverse risk factor independent of age, WBC counts, karyotypes, and mutation patterns. Bioinformatics analyses revealed that higher KIAA0125 expression was associated with hematopoietic and leukemic stem cell signatures and ATP-binding cassette transporters, two predisposing factors for chemoresistance.

scholarly journals Overexpression of the major vault transporter protein lung-resistance protein predicts treatment outcome in acute myeloid leukemia

Blood ◽  
1996 ◽  
Vol 87 (6) ◽  
pp. 2464-2469 ◽  
Author(s):  
AF List ◽  
CS Spier ◽  
TM Grogan ◽  
C Johnson ◽  
DJ Roe ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Prognostic Significance ◽  
Secondary Aml ◽  
Lung Resistance Protein ◽  
Transporter Protein ◽  
Lung Resistance ◽  
Resistance Protein ◽  
Acute Myeloid

The monoclonal antibody LRP56 recognizes a 110-kD major vault protein (lung-resistance protein [LRP]) overexpressed in several P-glycoprotein- negative (Pgp-), multidrug resistant tumor cell lines. To determine the frequency of LRP overexpression, its prognostic significance, and its relation to Pgp, we analyzed bone marrow specimens from 87 consecutive patients with acute leukemia. Diagnoses included de novo acute myeloid leukemia (AML; 21 patients), leukemia arising from an antecedent hematologic disorder or prior cytotoxic therapy (secondary AML; 27 patients), AML in relapse (29 patients), and blast phase of chronic myeloid leukemia (CML-BP; 10 patients). A granular cytoplasmic staining pattern was detected by immunocytochemistry in 32 (37%) cases, including 7 (33%) de novo AML, 13 (48%) secondary AML, 11 (38%) relapsed AML, and 1 of 10 CML-BP. Among 66 evaluable patients with AML, LRP overexpression was associated with an inferior response to induction chemotherapy (P = .0017). Remissions were achieved in 35% of LRP+ patients as compared with 68% of LRP- patients. Although Pgp adversely affected response in univariate analysis (P = .0414), only LRP had independent prognostic significance when compared in a logistic regression model (P = .0046). Differences in remission duration (P = .075) and overall survival (P = .058) approached significance only for LRP. Sequential specimens from remitting patients receiving treatment with the Pgp modulator cyclosporin-A showed emergence of the LRP phenotype despite a decrease or loss of Pgp at the time of treatment failure (P =.0304). Significant associations were observed between LRP and age greater than 55 years (P = .017), Pgp (P = .040), and prior treatment with mitoxantrone (P = .020) but not with CD34. These findings indicate that overexpression of the novel transporter protein LRP is an important predictor of treatment outcome in AML.

Update of the Modified Hyper-CVAD Regimen with or without Rituximab in Newly Diagnosed Adult Acute Lymphocytic Leukemia (ALL).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1831-1831 ◽  
Author(s):  
Deborah A. Thomas ◽  
Jorge Cortes ◽  
Susan O’Brien ◽  
Stefan Faderl ◽  
Farhad Ravandi ◽  
...  
Keyword(s):  
Disease Free Survival ◽  
Complete Response ◽  
The Elderly ◽  
Lymphocytic Leukemia ◽  
High Dose ◽  
Intensive Chemotherapy ◽  
Newly Diagnosed ◽  
Positive Group ◽  
Cd20 Expression ◽  
Laminar Air Flow

Abstract Hyper-CVAD is effective therapy for adult ALL [Kantarjian et al, JCO18:547, 2000; Kantarjian et al, Cancer101:2788, 2004]. Intensive chemotherapy with hyper-CVAD (fractionated cyclophosphamide, vincristine [VCR], doxorubicin and dexamethasone) was alternated with high dose methotrexate and cytarabine every 21 days for 8 courses with G-CSF and prophylactic antibiotics, followed by maintenance with POMP (6-MP, methotrexate, VCR, prednisone). Complete response (CR) rate was 92% with 3-year disease-free survival (DFS) rates 38% overall. A modified hyper-CVAD regimen was developed to address the following: (1) higher induction mortality in patients (pts) aged 60 or older (17% versus 3%); (2) longer DFS reported with early anthracycline intensification; (3) worse survival with CD20 expression (excluding Burkitt’s [BL] and lymphoblastic lymphoma [LL] subtypes); (4) CNS relapse rate of 6% and 1% in low and high risk pts, respectively and (5) late relapses after completion of therapy. Modifications to Hyper-CVAD Parameter Hyper-CVAD Modified Hyper-CVAD Laminar air flow rooms No For age ≥ 60 yrs or poor PS Dose-intensive anthracycline No C2 Liposomal DNR & cytarabine Rituximab No For CD20 ≥ 20 Intrathecal treatments 4–16 6–8 Maintenance (POMP) 2 years 3 years Intensifications (MTX, asparaginase) Months 7 & 11 Months 6,7 & 18,19 with hyper-CVAD Newly diagnosed or primary refractory (1 course only) pts were eligible. BL and Ph+ ALL pts were excluded. From May 2000 to December 2001, 77 pts were treated with the modified regimen detailed above (9 courses of intensive chemotherapy). The program was then modified further with elimination of course 2 anthracycline intensification. An additional 80 pts were treated with hyper-CVAD with or without rituximab (8 courses of intensive chemotherapy). The median age for these 157 pts was 40 yrs (range, 15–83) with 20% aged ≥ 60 yrs; 57% were males. Overall response rate was 94% in the evaluable pts (8 too early) with no difference by CD20 expression (49% were CD20+). No induction deaths were observed in the elderly subgroup (2 younger pts with induction deaths). Outcome with anthracycline intensification appeared worse, particularly in the CD20 negative group. The addition of rituximab appeared to improve DFS in CD20 positive group (with or without anthracycline intensification) compared with hyper-CVAD alone (2 yr DFS 90% versus 65%, p=.03); however, overall survival in the CD20 positive group was influenced by deaths in CR (10%) in elderly patients related to GNR sepsis or pneumonia during the intensive phase. Additional accrual and follow-up is needed to further define the role of rituximab in non-Burkitt’s adult ALL.

Long-Term Results of the GIMEMA LAP AIDA 0493 Amended Protocol in Elderly Patients with Acute Promyelocytic Leukemia (APL).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 885-885
Author(s):  
R. Latagliata ◽  
M. Breccia ◽  
P. Fazi ◽  
M. Vignetti ◽  
A. Cupri ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Risk Score ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Long Term Results ◽  
Induction Treatment ◽  
Prognostic Impact ◽  
Wbc Count

Abstract In order to reduce toxicity in elderly patients with newly diagnosed APL, since 3/1997 the Italian cooperative group GIMEMA evaluated an amended AIDA protocol for patients aged &gt; 60 years, consisting of the same induction with ATRA and Idarubicin but only 1st consolidation course (Idarubicin + Cytarabine), followed by 2 years maintenance with ATRA alone. Up to now, 56 patients (25 males and 31 females, median age 66.2 years, 46 with PS 0-1 and 10 with PS 2) are fully evaluable. At onset, according to GIMEMA-PETHEMA risk score, 18 were low-risk(32.5%), 31 intermediate risk (55%) and 7 high risk (12.5%). After induction treatment, 54 patients (96.4%) achieved CR and 2 (3.6%) died from haemorrhage (1) and infection (1). ATRA syndrome was documented in 5 patients (9.3%): 13/56 patients (23.2%) showed during induction other toxicities (WHO 3 – 4) not related to ATRA. After CR achievement, 2 patients died in CR from haemorrhage (1) and infection (1) and 52 received the consolidation course: on the whole, during consolidation 4 patients (7.6%) had a toxicity WHO 3 – 4 and 2 of them (3.8%) died from haemorrhage (1) and infection (1). The remaining 50 patients started maintenance treatment: up to now, 12 patients (22.2%) relapsed, after a median time from morphological CR of 19 months (range 7 – 86). Overall survival (OS) was 76.1% and 73.3% at 3 and 5 years, respectively. Disease free survival (DFS) was 64.5% and 61.3% at 3 and 5 years, respectively. At the univariate analysis, PS =2 (p=0.0019), WBC count &gt; 3 x 109 /l (p=0.018) and male gender (p=0.03) had a bad prognostic impact on DFS, while only PS=2 (p=0.05) did it on OS. Age, PLTS count, WBC count &gt; 10 x 109 /l, and risk score did not affect both OS and DFS. At the multivariate analysis on DFS, only PS =2 retained prognostic significance (HR = 3.8). In conclusion, the amended GIMEMA protocol has shown to be effective and safe in elderly APL patients, as the rate of death in CR was reduced when compared with previous results in not amended GIMEMA LAP AIDA 0493: however, to face with a relapse rate &gt; 20%, future strategies might be designed which exploit the use of more targeted approaches including combinations of ATRA, arsenic trioxide, and anti-CD33 monoclonal antibodies.

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