Benefits of the Intermittent Use of 6-Mercaptopurine and Methotrexate in Maintenance Treatment for Low-Risk Acute Lymphoblastic Leukemia in Children: Randomized Trial From the Brazilian Childhood Cooperative Group—Protocol ALL-99

2010 ◽  
Vol 28 (11) ◽  
pp. 1911-1918 ◽  
Author(s):  
Silvia R. Brandalise ◽  
Vitória R. Pinheiro ◽  
Simone S. Aguiar ◽  
Eduardo I. Matsuda ◽  
Rosemary Otubo ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Maintenance Treatment ◽  
Lymphoblastic Leukemia ◽  
Low Risk ◽  
Cooperative Group ◽  
Group 2 ◽  
Grade 3 ◽  
To Receive ◽  
Group 1

PurposeTo describe event-free survival (EFS) and toxicities in children with low-risk acute lymphoblastic leukemia (ALL) assigned to receive either continuous 6-mercaptopurine (6-MP) and weekly methotrexate (MTX) or intermittent 6-MP with intermediate-dose MTX, as maintenance treatment.Patients and MethodsBetween October 1, 2000, and December 31, 2007, 635 patients with low-risk ALL were enrolled onto Brazilian Childhood Cooperative Group for ALL Treatment (GBTLI) ALL-99 protocol. Eligible children (n = 544) were randomly allocated to receive either continuous 6-MP/MTX (group 1, n = 272) or intermittent 6-MP (100 mg/m2/d for 10 days, with 11 days resting) and MTX (200 mg/m2every 3 weeks; group 2, n = 272).ResultsThe 5-year overall survival (OS) and EFS were 92.5% ± 1.5% SE and 83.6% ± 2.1% SE, respectively. According to maintenance regimen, the OS was 91.4% ± 2.2% SE (group 1) and 93.6% ± 2.1% SE (group 2; P = .28) and EFS 80.9% ± 3.2% SE (group 1) and 86.5% ± 2.8% SE (group 2; P = .089). Remarkably, the intermittent regimen led to significantly higher EFS among boys (85.7% v 74.9% SE; P = .027), while no difference was seen for girls (87.0% v 88.8% SE; P = .78). Toxic episodes were recorded in 226 and 237 children, respectively. Grade 3 to 4 toxic events for groups 1 and 2 were, respectively, 273 and 166 for hepatic dysfunction (P = .002), and 772 and 636 for hematologic episodes (P = .005). Deaths on maintenance were: seven (group 1) and one (group 2).ConclusionThe intermittent use of 6-MP and MTX in maintenance is a less toxic regimen, with a trend toward better long-term EFS. Boys treated with the intermittent schedule had significantly better EFS.

Comparison of intermittent versus continuous methotrexate plus 6-mp in maintenance regimen for standard risk acute lymphoblastic leukemia in children (GBTLI ALL-99)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 9512-9512 ◽  
Author(s):  
S. R. Brandalise
Keyword(s):  
Maintenance Therapy ◽  
Maintenance Treatment ◽  
Risk Group ◽  
Lymphoblastic Leukemia ◽  
Treatment Schedule ◽  
Group 2 ◽  
Grade 3 ◽  
Standard Risk ◽  
Group 1

9512 Objectives: To compare by randomization the conventional use of 6-MP (50 mg/m2 daily) / MTX (25 mg/m2/wk) regimen with the intermittent use of MTX (200 mg/m2/IV 6 h infusion each 21 days)/ 6-MP (100 mg/m2/day × 10) in maintenance therapy. Methods: Newly diagnosed ALL children up to 18 yrs of age registered in the GBTLI ALL-99 Protocol. The eligibility criteria for standard-risk group were age >1 <9 years and WBC count at diagnosis <50,000/mm3 and good responders at D7/D14. Randomization was made after the late consolidation phase (week 42) prior to the maintenance treatment. Treatment Schedule: Induction: [DX(Pred), DNM, VCR, L-ASP, CICLO, Ara-C, 6-MP], Intensification: (MTX 2 g/m2 6 h inf. × 4, 6-MP) Late Consolidation: (DX, VCR, DOXO, L-ASP, CICLO, ARA-C, 6-TG) plus prolonged triple intratecal therapy, were done previously to maintenance therapy. Total treatment duration was two years. No CNS radiation was done. Toxicities were defined according to NCI-version 2001 criteria. Results: 560 pts were enrolled in the study. 22 slow responders pts (4.1%) moved to high risk group. The total number of analyzed pts was 512. Two hundred and thirty pts entered group 1 [continuous (conventional) 6MP-MTX] and 230 pts entered group 2 (Intermittent MTX/6-MP). Remission rate was 95.3%. 439 pts (87.9%) are in CCR. The mean follow up period is 2.2 years. The estimated 5 years OS rate for both groups is 88.1% ± 2.1%. The estimated 5 years EFS for both groups is 80% ± 2.9%. According to maintenance regimen, the 5 years EFS rate is 80.2% ± 4.5% and 88.3% ± 3.7% for group 1 and group 2, respectively (p=0.048). Grade 3 and 4 hepatic toxicities were 254 episodes for group 1 and 144 episodes for group 2 (p=0.019). Grade 3 CNS toxicities were 13 episodes (group 1) and 5 in group 2. Grade 4 hematological toxicities were 254 episodes for group 1 and 144 episodes for group 2 (p=0.003). Conclusions: Despite the short mean time follow-up (2.2 years) the patients with the intermittent regimen (Group 2) had better EFS rate (p = 0.048) and less hematological, CNS and hepatic toxicities, comparing with patients that received conventional maintenance treatment (group 1). No significant financial relationships to disclose.

scholarly journals Chemotherapy in 998 unselected childhood acute lymphoblastic leukemia patients. Results and conclusions of the multicenter trial ALL-BFM 86

Blood ◽  
1994 ◽  
Vol 84 (9) ◽  
pp. 3122-3133 ◽  
Author(s):  
A Reiter ◽  
M Schrappe ◽  
WD Ludwig ◽  
W Hiddemann ◽  
S Sauter ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Risk Group ◽  
Lymphoblastic Leukemia ◽  
Multicenter Trial ◽  
Low Risk ◽  
Event Free Survival ◽  
Free Survival ◽  
Risk Patients ◽  
To Receive

Abstract In trial ALL-BFM 86, the largest multicenter trial of the Berlin- Frankfurt-Munster (BFM) study group for childhood acute lymphoblastic leukemia (ALL), treatment response was used as an overriding stratification factor for the first time. In the previous trial ALL-BFM 83, the in vivo response to initial prednisone treatment was evaluated prospectively. A blast cell count of > or = 1,000/microL peripheral blood after a 7-day exposure to prednisone and one intrathecal dose of methotrexate (MTX) identified 10% of the patients as having a significantly worse prognosis. In trial ALL-BFM 86 patients with > or = 1,000/microL blood blasts on day 8 were included in an experimental branch EG. Patients with < 1,000/microL blood blasts on day 8 were stratified by their leukemic cell burden into two branches, Standard Risk Group (SRG) and Risk Group (RG). SRG patients received an eight- drug induction followed by consolidation protocol M (6-mercaptopurine, high-dose [HD] MTX 4 x 5 g/m2) and maintenance. RG patients were treated with an additional eight-drug reinduction element. For EG patients protocol M was replaced by protocol E (prednisone, HD-MTX, HD- cytarabine, ifosfamide, mitoxantrone). All patients received intrathecal MTX therapy; only those of branches RG and EG received cranial irradiation. In branch RG, patients were randomized to receive or not to receive late intensification (prednisone, vindesine, teniposide, ifosfamide, HD-cytarabine) in the 13th month. During the trial reinduction therapy was introduced in branch SRG, because in the follow-up of trial ALL-BFM 83 the randomized low-risk patients receiving reinduction did significantly better. Nine hundred ninety- eight evaluable patients were enrolled, 28.6% in SRG, 61.1% in RG, 10.3% in EG. At a median follow-up of 5.0 (range 3.4 to 6.9) years, the estimated 6-year event-free survival was 72% +/- 2% for the study population, 58% +/- 5% in branch SRG for the first 110 patients without reinduction therapy, 87% +/- 3% for the next 175 patients with reinduction therapy, 75% +/- 2% in branch RG, and 48% +/- 5% in branch EG. Late intensification did not significantly affect treatment outcome of RG patients; however, only 23% of the eligible patients were randomized. Prednisone poor response remained a negative prognostic parameter despite intensified therapy. The results confirmed the benefit of intensive reinduction therapy even for low-risk patients. The strategy of induction, consolidation, and intensive reinduction may offer roughly 75% of unselected childhood ALL patients the chance for an event-free survival.

scholarly journals 2699. Pneumococcal Vaccination During Chemotherapy in Children Treated for Acute Lymphoblastic Leukemia

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S949-S949
Author(s):  
Sarah Dorval ◽  
Léna Coïc ◽  
Denis Blais ◽  
Jean-Marie Leclerc ◽  
Caroline Laverdière ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Pneumococcal Infection ◽  
Pneumococcal Vaccination ◽  
Booster Vaccination ◽  
Maintenance Phase ◽  
Vaccination Schedule ◽  
Serum Samples ◽  
Group 2 ◽  
Group 1

Abstract Background Children undergoing therapy for acute lymphoblastic leukemia (ALL) are at high risk of invasive pneumococcal disease (IPD). Immunization with conjugated vaccines following chemotherapy is recommended for pediatric patients. In an attempt to provide an earlier protection against invasive pneumococcal infection, we aimed to assess immunity to S. pneumoniae among children vaccinated during chemotherapy for ALL. Methods We retrospectively analyzed the rate of seroprotection among ALL children treated in our institution in accordance with the DFCI ALL Consortium protocol between 2007 and 2014. A pneumococcal conjugate vaccine (PCV) booster was given to all subjects after the end of chemotherapy (groups 1 and 2). In group 2, a PCV dose was also administered during the maintenance phase. Clinical characteristics as well as individual immunization records were collected from our local immunization database. All children were up to date with their vaccination schedule at diagnosis. Serum samples were obtained on a routine follow-up visit, after the end of chemotherapy and after the PCV vaccine booster to measure serotype-specific IgG pneumococcal antibodies. Antibody level ≥0.35µg/mL was considered protective. Patients with seroprotective antibodies level for ≥ 50% of serotypes contained in vaccines were defined as seroprotected. Results 62 children [34 girls (54.8%)] were included in the analysis. Median age at diagnosis was 45 months (range:12–160). At the end of chemotherapy, 34.2% of children in group 1 (13/38) and 79.2% in group 2 (19/24) were seroprotected (P < 0.01). Median interval of time between the end of chemotherapy and the PCV booster vaccination was 6 months (range: 2–64 months). After PCV-13 booster, the rate of seroprotection raised to 100% (38/38) in group 1 and 91.7% in group 2 (22/24). Conclusion Rates of pneumococcal seroprotected children treated for ALL are low at the end of chemotherapy. However, PCV booster during chemotherapy could be useful to increase the level of seroprotection and shorten the period of susceptibility to IPD. After chemotherapy for ALL, children benefit from a PCV booster to enhance seroprotection. Disclosures All authors: No reported disclosures.

Therapy Related Acute Lymphoblastic Leukemia: Pethema Experience

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4994-4994
Author(s):  
Nicholas John Kelleher ◽  
David Gallardo ◽  
Salut Brunet ◽  
Pau Montesinos ◽  
Josep-Maria Ribera ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
De Novo ◽  
Lymphoblastic Leukemia ◽  
Cytotoxic Therapy ◽  
Survival Group ◽  
Significant Difference ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Abstract Background Therapy related acute lymphoblastic leukemia, a subset of secondary acute lymphoblastic leukemia has been estimated as accounting for between 1.2 and 6.9% of all adult acute lymphoblastic leukemia cases. It has been associated with an increased frequency of high risk cytogenetic alterations and with worse clinical outcomes. It has been suggested these patients should be included in high risk treatment protocols. Method In order to evaluate these characteristics in a group of similar patients we contacted centres working within the PETHEMA group to request data on patients diagnosed with ALL asking for clinical information including the presence or absence of previous neoplasia and of previous cytotoxic therapy along with treatment responses and survival data. Results We received information on 429 patients of whom 22 had received cytotoxic therapy for a prior neoplasm.Patients were divided into group 1 with prior cytotoxic therapy, group 2 with prior neoplasia without cytotoxic therapy and group 3 de novo ALL. We found patients in group 3 to be younger than the other two groups Group 1( 55 years) Group 2 (65 years) Group 3 (34 years) (p=0.001). No statistically significant difference was shown for white cell count, cytopenias, CNS involvement, LDH or for B versus T immunophenotype. Nor did our series show a significant difference in the frequencies of high risk cytogenetics between the groups. Figures for complete remission [Group 1- 13 (93%); Group 2- 6 (75%); Group 3-346 (85%) p=0.477] were higher in group 1 therapy related ALL compared with de novo patients without reaching clinical significance. Nor was a statistically significant difference shown for 3 year overall survival [Group 1 (80%); Group 2 (38%); Group 3 (47%) p=0.151] , 3 year event free survival [Group 1 (67%); Group 2 (38%); Group 3 (42%) p=0.24] or for complete remission duration [Group 1 (75%);Group 2 (50%); Group 3 (60%) p=0.462] Conclusion Apart from age, our series did not show an increase in poor risk clinical or cytogenetic features in therapy related ALL patients compared with de novo disease cases and nor was clinical outcome demonstrated to be worse. This would suggest that risk stratification should be carried out using currently recognized parameters without specifically taking into account the status of therapy related disease. Disclosures: No relevant conflicts of interest to declare.

Predictive Value of Minimal Residual Disease: Analysis By Flow-Cytometry in Children with Relapsed Acute Lymphoblastic Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2494-2494
Author(s):  
Myriam Ruth Guitter ◽  
Jorge Gabriel Rossi ◽  
Elisa Sajaroff ◽  
Carolina Carrara ◽  
Pizzi Silvia ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
P Value ◽  
Time Points ◽  
Group 3 ◽  
Group 2 ◽  
To Receive ◽  
Group 1

Abstract Introduction: Despite the advances observed in the outcome of pediatric acute lymphoblastic leukemia (ALL) treatment during the last 20 years, relapse remains the most common cause of treatment failure in childhood ALL. Several factors have been associated to the prognosis of these patients; however, minimal residual disease (MRD) emerges as a relevant predictor of outcome. Objectives: The aims of this study were to assess MRD by flow-cytometry in relapsed ALL and to evaluate its prognostic impact as a predictor factor of outcome at the end of the induction therapy and prior to hematopoietic stem cell transplantation (HSCT). Patients and Methods: From Aug'10 to Jun'15, 123 ALL patients were treated at our center. MRD determination at least at two time-points during relapse treatment was a requirement for considering a patient eligible for the present study. Sixty-six cases were excluded due to the following causes: 10 patients died during induction, 2 died early in complete remission (CR), 29 did not respond to chemotherapy, in 13 patients MRD determination was not performed: 4 did not have clinical data available, 4 patients were Down Syndrome and 4 children received treatment for relapse in other centers. Thus, fifty-seven patients achieved CR and were evaluated for MRD at two time points. Of them, 56 patients belonged to S4 and S3 and 1 patient to S1 group as defined by the Berlin-Frankfurt-Münster stratification for relapsed ALL. MRD was analyzed by multiparametric flow-cytometry following ALL-IC 2009 guidelines. Negative MRD was defined as disclosing less than 0.1% of blasts. For this analysis, patients were stratified based on MRD levels at two different time points: after end of induction, before HSCT or at any other time point during the follow-up for patients who did not undergo HSCT. Three groups were defined: Group-1: negative at both time points (n= 23), Group-2: positive at 1 time point (n= 13) and Group-3: positive at both time points (n= 21). Patients who relapsed before receiving HSCT were considered Group-3. Twenty-five patients underwent HSCT: 13 of them from Group-1, 9 from Group-2 (2 had positive MRD previous to receive HSCT) and 3 patients from Group-3. HSCT was performed with matched familiar donor in 16 cases and matched unrelated donor in 9 cases. Results: The distribution of events according to receiving or not HSCT was: 5 died due to transplant related mortality (TRM), 9 relapsed after receiving HSCT and 16 during treatment with chemotherapy. With a median follow-up of 16 (range: 6-67) months, overall 3-year EFS probability (EFSp) (SE) was 32 (8)%. The 3-year EFSp was 75 (11)% for Group-1, 24 (14)% for Group-2 and 0% for Group-3 (p-value <0.00001). Comparing patients who did not receive HSCT vs. patients who did, EFSp (SE) was 32 (12)% and 29 (11)% respectively (p-value: non-significant). The EFSp (SE) according to MRD groups in patients who underwent HSCT was: Group-1: 53 (19)%, Group-2: 14 (13)% and 0% for Group-3 (p-value: 0.06). Conclusions: MRD quantification by flow-cytometry demonstrated to be a significant prognostic factor for relapsed ALL. Both, TRM and death in CR rates, were high and should be decreased by improving supportive measures. MRD determination by flow-cytometry in patients who underwent HSCT showed a trend to achieve a better EFSp, thus representing a relevant tool for stratifying relapsed ALL patients in order to achieve a better selection of patients to receive HSCT. Disclosures No relevant conflicts of interest to declare.

Survival Trends in Adult T-Acute Lymphoblastic Leukemia / Lymphoma (ALL), a Comparative Analysis of 92 Patients By Year of Diagnosis

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2490-2490
Author(s):  
Hassan B Alkhateeb ◽  
Tasha Lin ◽  
Moussab Damlaj ◽  
Aref Al-Kali ◽  
Naseema Gangat ◽  
...  
Keyword(s):  
Overall Survival ◽  
Comparative Analysis ◽  
Acute Lymphoblastic Leukemia ◽  
Research Funding ◽  
Lymphoblastic Leukemia ◽  
Autologous Transplantation ◽  
Cell Transplant ◽  
Patient Groups ◽  
Group 2 ◽  
Group 1

Abstract Background: Adult T-cell acute lymphoblastic leukemia / lymphoma (T-ALL) is an rare and aggressive hematological malignancy with overall survival (OS) according to the UKALL XII/E2993 of 48% at 5 years (Marks et al, Blood 2009). Over the last decade, the incorporation of L-asparaginase, dose intensification (similar to pediatric protocols), availability of newer agents such as clofarabine (Dec 2004) and nelarabine (Oct 2005) have been shown to improve outcomes. We carried out this study to see if the above mentioned changes in treatment have translated to an OS benefit. Methods: After due IRB approval, adults diagnosed with T-ALL from 1990-2014 at Mayo Clinic were identified. All clinical and pathologic data was retrospectively reviewed Comparative analysis was performed based on year of diagnosis before and after 2005 (Group 1, diagnosis prior to 2005, and Group 2, diagnosis post 2005). Survival was estimated using the Kaplan-Meier Method and log-rank test. Chi-square test was used to compare variables. Results: A. Patient Characteristics: Between 1990 and 2014, a total of 92 consecutive patients (pts) with T-ALL were identified. Median age at diagnosis was 33 years (range; 18-88 years) with 72% males. Distribution of pts by year of diagnosis was as follows: Group 1(n= 47) (51%), and Group 2 (n=45) (49%). Median overall survival was 97.2 months. Median follow up for Group 1 was 50 months, during which time 23 (39%) deaths were documented, and 22.8 months (0.9 - 115.4) for Group 2 at which time19 deaths (42%) were documented (p= 0.04). Pts in Group 2 were older than Group1 (median age 41 vs 27 years (p= 0.004). Apart from age, the two groups were similar in other characteristics (Table 1). B. Therapy received by patient groups: We observed a high use of L-asparaginase containing regimens in Group 1 vs Group 2 [35(74%) pts vs 19 (42%), p=0.0013]. In contrast there was an increase in use of Hyper-CVAD in Group 2; 23(51%) vs. 3 (6%) (p<0.0001). There was no difference in the use of intensive pediatric protocols (p=0.11). There was a trend of increased use of nelarabine in Group 2, however clofarabine usage was not different (p=0.09, and p=0.6 respectively) (Table1). Allogenic stem cell transplant was offered more in Group 2 compared to Group 1, 16 (36%) patients vs. 10 (21%) patients (p=0.0009). In contrast, 7 (19%) patients underwent autologous transplantation in group 1 vs. none in group 2 (p=0.0009). C. Overall outcome by patient groups: We did not observe any difference in CR, or relapse rates among the two groups. The median OS and time to relapse were also not statistically different among Group 1 and 2 [102.6 vs 61.8 months Figure A, and 7.1 vs 14.1 months respectively]. Furthermore, age adjusted survival analysis was also not statistically significant. Conclusion: In this large cohort of adult T-ALL patients, in spite of significant advances in treatment strategies over the last two decades, we observed no difference in overall and relapse free survival prior to and after 2005. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Al-Kali: Celgene: Research Funding. Thompson:Kite Pharma: Research Funding. Witzig:Spectrum: Research Funding; Novartis: Research Funding; Celgene: Research Funding; Amgen: Honoraria; Valeant Pharma: Equity Ownership.

NUDT15 genetic variants are related to thiopurine-induced neutropenia in Thai children with acute lymphoblastic leukemia

2020 ◽  
Vol 21 (6) ◽  
pp. 403-410
Author(s):  
Apichaya Puangpetch ◽  
Rawiporn Tiyasirichokchai ◽  
Samart Pakakasama ◽  
Supaporn Wiwattanakul ◽  
Usanarat Anurathapan ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Maintenance Therapy ◽  
Therapy Group ◽  
Lymphoblastic Leukemia ◽  
Wild Type ◽  
Homozygous Variant ◽  
Heterozygous Variant ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Aim: 6-Mercaptopurine (6MP) is key to the treatment of acute lymphoblastic leukemia (ALL) as part of maintenance therapy. NUDT15 was identified as a novel thiopurine regulator conferring 6MP sensitivity. The aim of this study was to evaluate the influence of NUDT15 variants on 6MP-induced neutropenia in Thai children with ALL. Materials & methodology: Genotyping of NUDT15 (c.415C>T; rs116855232) and c.36_37insGGAGTC; rs554405994) was performed by Sanger sequencing in 100 patients with ALL. Patients were classified into wild-type (group 1), heterozygous variant (group 2) and homozygous variant (group 3). Clinical and laboratory features during the first 6 months of maintenance therapy were investigated. Therapy-induced neutropenia was observed in 31 patients during the weeks 1–8 (early myelotoxicity), while therapy-induced neutropenia was observed in 47 patients during the weeks 9–24 (late myelotoxicity). Results: There were 85 wild-type patients, 14 heterozygous variant patients and one homozygous variant patient. NUDT15 variants were associated with neutropenia as compared with wild-type (odds ratio: 17.862; 95% CI: 4.198–75.992, padj = 9.5 × 10-5). Multivariate analysis showed that the low-risk group was associated with neutropenia (p = 0.014) in the first 8 weeks of 6MP therapy. Group 2 and group 3 patients had significantly lower absolute neutrophil counts compared with group 1. The adjusted dose during the first 6 months of maintenance therapy with NUDT15 genotype group 1, 2 and 3 were 50, 36.6 and 12.5 mg/m2/day, respectively. Conclusion: Taken together, our results indicate NUDT15 variants may cause neutropenia, and the 6MP dosage should be considered in patients according to the NUDT15 variants to inform personalized 6MP therapy.

Adult acute lymphoblastic leukemia: a multicentric randomized trial testing bone marrow transplantation as postremission therapy. The French Group on Therapy for Adult Acute Lymphoblastic Leukemia.

1993 ◽  
Vol 11 (10) ◽  
pp. 1990-2001 ◽  
Author(s):  
D Fière ◽  
E Lepage ◽  
C Sebban ◽  
C Boucheix ◽  
C Gisselbrecht ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Lymphoblastic Leukemia ◽  
Maintenance Chemotherapy ◽  
Adult Acute Lymphoblastic Leukemia ◽  
Postremission Therapy ◽  
To Receive ◽  
Group 1

PURPOSE In a prospective multicenter study, we analyzed the benefits of allogeneic bone marrow transplantation (BMT) in a nonselected group of adult patients with acute lymphoblastic leukemia (ALL) and, by a randomized trial, evaluated the effectiveness of autologous BMT over chemotherapy as postremission therapy in patients younger than 50 years who were not candidates for allogeneic BMT. PATIENTS AND METHODS After induction therapy that randomized patients to receive one of two anthracycline-containing regimens, either daunorubicin (DNR) or zorubicin (ZRB), patients were assigned to postremission treatment according to age and results of HLA typing. Patients younger than 40 years with an HLA-identical sibling (group 1) were scheduled to receive cyclophosphamide 60 mg/kg on days 1 and 2, total-body irradiation (TBI), and allogeneic BMT. Patients older than 50 years (group 2) received the chemotherapy arm composed of three monthly consolidation courses (DNR or ZRB, cytarabine, and asparaginase) followed by maintenance chemotherapy (modified L10 regimen). The remaining population (group 3) was randomly assigned to receive, after the three 1-month consolidation courses, either the chemotherapy arm or autologous BMT following a conditioning regimen similar to that of group 1. RESULTS Of the 572 assessable patients, 436 achieved complete remission (78% +/- 2% for DNR v 74% +/- 3% for ZRB; P = .3). The estimated 3-year disease-free survival (DFS) rate for the 116 patients included in group 1 was 43% +/- 5%. Both autologous BMT (95 patients) and chemotherapy (96 patients) produced comparable 3-year DFS rates (39% +/- 5% v 32% +/- 5%) and survival durations (49% +/- 5% v 42% +/- 5%). However, late relapses after 36 months were mainly observed in the chemotherapy arm. CONCLUSION This first interim analysis did not demonstrate a benefit of this autologous BMT procedure over classical maintenance chemotherapy in patients with ALL who received consolidation chemotherapy.

Abstract 901: Impact of Microvascular Dysfunction on Long-Term Cardiovascular Events after Primary Coronary Intervention for Acute Myocardial Infarction in Patients Achieving TIMI Grade 3 Reperfusion

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Koichi Tamita ◽  
Atsushi Yamamuro ◽  
Syuichiro Kaji ◽  
Minako Katayama ◽  
Tomoko Tani ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Microvascular Dysfunction ◽  
Coronary Intervention ◽  
Cardiovascular Outcomes ◽  
Timi Grade ◽  
Group 2 ◽  
Grade 3 ◽  
Group 1

It has been reported that even if TIMI 3 flow is achieved in epicardial coronary arteries after primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI), microvascular dysfunction results in insufficient reperfusion. Recent studies have shown that microvascular injury can be assessed from coronary flow velocity (CFV) pattern. The aim of this prospective study was to examine whether the CFV pattern predicts the long-term cardiovascular outcomes in AMI patients who achieved TIMI grade 3 reperfusion. The study population consisted of 161 consecutive patients with a first anterior AMI successfully treated with primary PCI (≤50% residual stenosis with TIMI grade 3). We examined the CFV pattern immediately after PCI using a Doppler guidewire. We defined microvascular dysfunction as a diastolic deceleration time ≤600 ms and the presence of systolic flow reversal. Patients were divided into two groups: those without microvascular dysfunction (n=126; group 1) and those with micriovascular dysfunction (n=35; group 2). We evaluated the association between the microvascular dysfunction and the long-term major adverse cardiovascular event (MACE) rates. The Kaplan-Meier survival curves showed that group 2 was poorer than group 1 in prognosis (p=0.0014). Risk-adjusted data by multivariate analysis showed that the microvascular dysfunction was the strongest predictor for long-term MACE (hazard ratio: 3.37; 95% CI, 1.59–7.15; p=0.0015). The CFV pattern immediately after PCI is an accurate predictor of the long-term cardiovascular outcomes in patients with AMI who achieved TIMI grade 3 reperfusion.

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