Low Dose Decitabine Versus Best Supportive Care in Elderly Patients with Intermediate or High Risk MDS Not Eligible for Intensive Chemotherapy: Final Results of the Randomized Phase III Study (06011) of the EORTC Leukemia and German MDS Study Groups

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 226-226 ◽  
Author(s):  
Pierre WijerMans ◽  
Stefan Suciu ◽  
Liliana Baila ◽  
Uwe Platzbecker ◽  
Aristoteles Giagounidis ◽  
...  
Keyword(s):  
High Risk ◽  
Supportive Care ◽  
Disease Progression ◽  
Low Dose ◽  
Phase Iii ◽  
Intensive Chemotherapy ◽  
Free Survival ◽  
Phase Iii Study ◽  
The Difference ◽  
Grade 3

Abstract Introduction: In 2002 the EORTC and the German MDS Study Group initiated a randomized phase III study comparing low dose Decitabine to supportive care in patients (pts) of 60 years or older with primary or secondary MDS or CMML. MDS patients with either 11–20% BM blasts or ≤ 10% blasts and poor cytogenetics could be included. Pts with a BM blast count between 21–30% without signs of disease progression for at least one month were also candidates for the study. Methods: Patients were centrally randomized; stratification factors were cytogenetics risk group, IPSS, MDS (primary vs secondary) and study centre, The treatment schedule was 15 mg/m2 Decitabine i.v. over 4 hours every 8 hours for the first 3 three consecutive days, of every 6 week-cycle, for a maximum of 8 cycles. Results were evaluated every 2nd cycle. When a complete remission was reached at least another 2 courses were given. The primary endpoint of the study was Overall Survival. AML free survival, Progression Free Survival (PFS), response rate, toxicity and QoL were secondary endpoints. A total of 185 deaths were required to detect a hazard ratio (HR) of 0.66 (alpha=5%, beta=20%). Intent-to-treat analysis was used. Results: Between 10.2002 and 5.2007 a total of 233 pts (149 male and 84 female) were recruited from 40 centres. The median age was 70 (60–90 years); RAEB-t was diagnosed in 32% of the pts. Most pts had an IPSS Intermediate-2 (55%) or high risk (38%). Poor risk cytogenetics was found in 46% of the patients. Prior therapy for MDS (not being intensive chemotherapy) was given in 20% of pts. The randomized groups were well balanced regarding stratification factors, age and FAB classification. The median follow up was 2.5 years. Time to Off Study was 180 (Decitabine) vs 112 days (SC arm). The median number of cycles given to the patients was 4 with 40%getting no more than 2 cycles. In a significant number of pts, subsequent treatment, consisting of transplant (10%) or induction chemotherapy (11%), was given. The distribution of best response in Decitabine vs SC arm was CR (13% vs 0%), PR (6% vs 0%), HI (15% vs 2%), SD (14% vs 22%), PD (29% vs 68%), hypoplasia (14% vs 0%), inevaluable (8% vs 8%). The 18 pts on Decitabine with a HI showed the following responses: 3-lineage (n=7), 2-lineage (n=5) and 1-lineage (n=6). The median time to response (CR/PR/HI) was 0.32 yrs and the response duration was 0.72 years. Median OS was 0.84 (Decitabine) vs 0.71 years (SC arm), estimated HR was 0.88, 95% CI 0.66–1.17, p=0.38 (logrank 2-sided). The PFS was significantly (p=0.004) longer in Decitabine vs SC arm: median was 0.55 vs 0.25 years, HR=0.68 (95% CI 0.52–0.88). Time to AML or Death was not significantly improved (p=0.24): median was 0.73 vs 0.51 years (HR=0.85, 95% CI 0.64–1.12). Toxicity. The toxicity was mainly cytopenia related toxicity that was either disease related or hematotoxicity; CTC grade 3–4 febrile neutropenia was 26% (Decitabine) vs 7% (SC arm) and Grade 3–4 infection was 59% vs 47%. Differences in non hematologic toxicities were mainly gastrointestinal: grade 1–2 nausea (28% vs 16%) and grade 1–2 vomiting (16% vs 9%). During the study period, 29 (Decitabine) vs 25 (SC arm) patients died: due to either progression to MDS/AML (7 vs 20), toxicity (9 vs 0), progression and/or toxicity (10 vs 1), other reasons (3 vs 4). Conclusions. Decitabine was found to be an effective drug in these high risk MDS patients with a overall RR of 34%, (similar to earlier studies), leading to a significant PFS improvement as compared to SC arm. The difference Decitabine vs SC arm regarding time to AML or Death was not significant. Due to shorter treatment duration (not being continued beyond 8 cycles) and maybe also due to subsequent treatments administered after disease progression, the difference regarding OS was lower (HR=0.88) and not statistically significant.

Low-Dose Decitabine Versus Best Supportive Care in Elderly Patients With Intermediate- or High-Risk Myelodysplastic Syndrome (MDS) Ineligible for Intensive Chemotherapy: Final Results of the Randomized Phase III Study of the European Organisation for Research and Treatment of Cancer Leukemia Group and the German MDS Study Group

2011 ◽  
Vol 29 (15) ◽  
pp. 1987-1996 ◽  
Author(s):  
Michael Lübbert ◽  
Stefan Suciu ◽  
Liliana Baila ◽  
Björn Hans Rüter ◽  
Uwe Platzbecker ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Supportive Care ◽  
Low Dose ◽  
Progression Free Survival ◽  
Best Supportive Care ◽  
Phase Iii ◽  
Intensive Chemotherapy ◽  
Free Survival ◽  
Patient Reported ◽  
Grade 3

Purpose To compare low-dose decitabine to best supportive care (BSC) in higher-risk patients with myelodysplastic syndrome (MDS) age 60 years or older and ineligible for intensive chemotherapy. Patients and Methods Two-hundred thirty-three patients (median age, 70 years; range, 60 to 90 years) were enrolled; 53% had poor-risk cytogenetics, and the median MDS duration at random assignment was 3 months. Primary end point was overall survival (OS). Decitabine (15 mg/m2) was given intravenously over 4 hours three times a day for 3 days in 6-week cycles. Results OS prolongation with decitabine versus BSC was not statistically significant (median OS, 10.1 v 8.5 months, respectively; hazard ratio [HR], 0.88; 95% CI, 0.66 to 1.17; two-sided, log-rank P = .38). Progression-free survival (PFS), but not acute myeloid leukemia (AML) –free survival (AMLFS), was significantly prolonged with decitabine versus BSC (median PFS, 6.6 v 3.0 months, respectively; HR, 0.68; 95% CI, 0.52 to 0.88; P = .004; median AMLFS, 8.8 v 6.1 months, respectively; HR, 0.85; 95% CI, 0.64 to 1.12; P = .24). AML transformation was significantly (P = .036) reduced at 1 year (from 33% with BSC to 22% with decitabine). Multivariate analyses indicated that patients with short MDS duration had worse outcomes. Best responses with decitabine versus BSC, respectively, were as follows: complete response (13% v 0%), partial response (6% v 0%), hematologic improvement (15% v 2%), stable disease (14% v 22%), progressive disease (29% v 68%), hypoplasia (14% v 0%), and inevaluable (8% v 8%). Grade 3 to 4 febrile neutropenia occurred in 25% of patients on decitabine versus 7% of patients on BSC; grade 3 to 4 infections occurred in 57% and 52% of patients on decitabine and BSC, respectively. Decitabine treatment was associated with improvements in patient-reported quality-of-life (QOL) parameters. Conclusion Decitabine administered in 6-week cycles is active in older patients with higher-risk MDS, resulting in improvements of OS and AMLFS (nonsignificant), of PFS and AML transformation (significant), and of QOL. Short MDS duration was an independent adverse prognosticator.

Phase III Trial of Infusional Fluorouracil, Leucovorin, Oxaliplatin, and Irinotecan (FOLFOXIRI) Compared With Infusional Fluorouracil, Leucovorin, and Irinotecan (FOLFIRI) As First-Line Treatment for Metastatic Colorectal Cancer: The Gruppo Oncologico Nord Ovest

2007 ◽  
Vol 25 (13) ◽  
pp. 1670-1676 ◽  
Author(s):  
Alfredo Falcone ◽  
Sergio Ricci ◽  
Isa Brunetti ◽  
Elisabetta Pfanner ◽  
Giacomo Allegrini ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Peripheral Neurotoxicity ◽  
Phase Iii Trial ◽  
Free Survival ◽  
Secondary Resection ◽  
Phase Iii Study ◽  
Grade 3

Purpose The Gruppo Oncologico Nord Ovest (GONO) conducted a phase III study comparing fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI [irinotecan 165 mg/m2 day 1, oxaliplatin 85 mg/m2 day 1, leucovorin 200 mg/m2 day 1, fluorouracil 3,200 mg/m2 48-hour continuous infusion starting on day 1, every 2 weeks]) with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI). Methods Selection criteria included unresectable metastatic colorectal cancer, age 18 to 75 years, and no prior chemotherapy for advanced disease. The primary end point was response rate (RR). Results A total of 244 patients were randomly assigned. An increase of grade 2 to 3 peripheral neurotoxicity (0% v 19%; P < .001), and grade 3 to 4 neutropenia (28% v 50%; P < .001) were observed in the FOLFOXIRI arm. The incidence of febrile neutropenia (3% v 5%) and grade 3 to 4 diarrhea (12% v 20%) were not significantly different. Responses, as assessed by investigators, were, for FOLFIRI and FOLFOXIRI, respectively, complete, 6% and 8%; and partial, 35% and 58%, (RR, 41% v 66%; P = .0002). RR confirmed by an external panel was 34% versus 60% (P < .0001). The R0 secondary resection rate of metastases was greater in the FOLFOXIRI arm (6% v 15%; P = .033, among all 244 patients; and 12% v 36%; P = .017 among patients with liver metastases only). Progression-free survival (PFS) and overall survival (OS) were both significantly improved in the FOLFOXIRI arm (median PFS, 6.9 v 9.8 months; hazard ratio [HR], 0.63; P = .0006; median OS, 16.7 v 22.6 months; HR, 0.70; P = .032). Conclusion The FOLFOXIRI regimen improves RR, PFS, and OS compared with FOLFIRI, with an increased, but manageable, toxicity in patients with metastatic colorectal cancer with favorable prognostic characteristics. Further studies of FOLFOXIRI in combination with targeted agents and in the neoadjuvant setting are warranted.

Randomized phase II trial of concomitant CT/RT versus TPF followed by concomitant CT/RT in locally advanced squamous cell carcinoma of the head and neck (LASCCHN)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5518-5518 ◽  
Author(s):  
A. Paccagnella ◽  
A. Buffoli ◽  
H. Koussis ◽  
P. D’Amanzo ◽  
L. Loreggian ◽  
...  
Keyword(s):  
Standard Treatment ◽  
Locally Advanced ◽  
Phase Iii ◽  
Serious Adverse Events ◽  
Randomized Phase Ii ◽  
Phase Iii Study ◽  
The Difference ◽  
Grade 3 ◽  
Toxicity Pattern ◽  
Pathological Cr

5518 Background: Concomitant CT/RT is the standard treatment for LASCCHN. Induction chemotherapy followed by CT/RT vs CT/RT alone have not yet been compared. The feasibility of TPF followed by CT/RT has been evaluated in a previous study (Int J Rad Oncol Biol Phys 2004, 59:481). Methods: Pts with inoperable stage III-IVa, PS 0–1, were randomized to CT/RT [2 cycles of Cisplatin 20 mg/sqm days 1–4, 5FU 800 mg/sqm 96 hours c.i. weeks 1 and 6 during RT (66–70 Gy)] (Arm A) or 3 cycles of neoadjuvant TPF (Docetaxel 75mg/sqm day1, Cisplatin 80mg/sqm day1, 5FU 800mg/sqm 96 hours c.i) followed by the same CT/RT (Arm B). Pts were stratified according to tumor site, T stage and nodal status. Neck dissection was performed in N2-N3 patients with pathological CR on primary tumor. The planned sample size was 96 pts to detect a difference in CR (primary endpoint) up to 15% in favour of arm B. The radiological responses were evaluated by an internal committee according to RECIST criteria. Results: Preliminary data are available for 84/96 randomized pts (42 arm A, 42 arm B). Pts/tumor characteristics are well balanced in the two arms. Toxicities during induction TPF consisted primarily of G3–4 granulocytopenia 56% (febrile neutropenia: 7.5%). Grade 3–4 toxicities during CT/RT in arm A and B were mucositis (42% and 26%), dysphagia (20% and 9%), skin reaction (12% and 8.6%), asthenia (5% and 3%); G3 weight loss (2% and 3%), G3 dry-mouth (0% and 3%). Duration of CT/RT was equivalent: 6.1 wks (4.2–8.7) in arm A and 6.3 wks (3.8–9.5) in arm B. At the end of CT/RT, in the 82 pts evaluable for efficacy, radiological CR were 20% (95% CI 8–37%) in arm A and 64% (95% CI 45–80%) in arm B. Conclusions: Three cycles of neoadjuvant TPF are feasible and don’t compromise subsequent concomitant CT/RT with comparable toxicity pattern. At the end of the treatment sequence serious adverse events were 31% in arm A and 34% in arm B. The difference in CR of 40% in favour of arm B justifies the following phase III study. Final results including pCR and DFS will be presented at the meeting. [Table: see text]

Phase III study of doxorubicin-cyclophosphamide followed by paclitaxel or docetaxel given every 3 weeks or weekly in operable breast cancer: Results of Intergroup Trial E1199

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 516-516 ◽  
Author(s):  
J. A. Sparano ◽  
M. Wang ◽  
S. Martino ◽  
V. Jones ◽  
E. Perez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Disease Free Survival ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Axillary Lymph ◽  
Free Survival ◽  
Significant Difference ◽  
Phase Iii Study ◽  
Grade 3

516 Background: Evidence suggests that docetaxel is more effective than paclitaxel, and paclitaxel is more effective when given weekly than every 3 weeks in metastatic breast cancer (BC). Methods: Eligibility included axillary lymph node positive or high-risk (tumor at least 2 cm) node-negative BC. All patients received 4 cycles of AC (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2) every 3 weeks, followed by either: (1) paclitaxel 175 mg/m2 every 3 weeks × 4 (P3), (2) paclitaxel 80 mg/m2 weekly × 12 (P1), (3) docetaxel 100 mg/m2 every 3 weeks × 4 (D3), or (4) docetaxel 35 mg/m2 weekly × 12 (D1). The primary comparisons included taxane (P vs. D) and schedule (every 3 weeks vs. weekly), and secondary comparisons included P3 vs. other arms. The trial had 86% power to detect a 17.5% decrease in disease-free survival (DFS) for either primary comparison, and 80% power to detect a 22% decrease for the secondary comparisons (2-sided nomimal 5% level tests corrected for multiple comparisons). Results: A total of 4,950 eligible patients were accrued. There was no difference in the primary comparisons afer 856 DFS events and 483 deaths after a median follow-up of 46.5 months at the 4th interim analysis ( www.sabcs.org , abstract 48). This is the final pre-specified analysis for the primary comparisons after 1,042 DFS events and 650 deaths (with 1,020 DFS events at this time, to be updated at the meeting). After a median followup of 60.2 months, there remains no significant difference in the hazard ratio (HR) for the taxane (1.02; p=0.73) or schedule (1.07; p=0.30) (as in the first analysis). In secondary comparisons of the standard arm (P3) with the other arms (HR > 1 favoring the experimental arms), the HRs were 1.30 (p = 0.003) for arm P1, 1.24 (p=0.02) for arm D3, and 1.09 (p=0.33) for arm D1. Analysis of interaction by hormone-receptor status will be presented. The incidence of worst grade toxicity (grade 3/4) was 24%/6% for arm P3, 24%/3% for arm P1, 21%/50% for arm D3, and 38%/6% for arm D1. Conclusions: There were no differences in DFS when comparing taxane or schedule overall. DFS was significantly improved in the weekly paclitaxel and every 3-week docetaxel arms compared with the every 3-week paclitaxel arm. [Table: see text]

Adjuvant therapy with pegylated interferon alfa-2b (36 months) versus low-dose interferon alfa-2b (18 months) in melanoma patients without macro-metastatic nodes: EADO trial.

2010 ◽  
Vol 28 (18_suppl) ◽  
pp. LBA8506-LBA8506 ◽  
Author(s):  
J. J. Grob ◽  
T. Jouary ◽  
B. Dreno ◽  
R. Gutzmer ◽  
A. Hauschild ◽  
...  
Keyword(s):  
Adjuvant Therapy ◽  
Low Dose ◽  
Pegylated Interferon ◽  
Interferon Alfa ◽  
Phase Iii ◽  
Type I ◽  
Duration Of Treatment ◽  
Free Survival ◽  
Pegylated Interferon Alfa ◽  
Grade 3

LBA8506 Background: Adjuvant therapy with low-dose adjuvant interferon alfa-2b (IFN) as well as with pegylated interferon alfa-2b (PEG-IFN) were both shown to be superior to observation in melanoma (M) patients (pts) without macro-metastatic nodes. However, the two strategies have never been assessed head to head. Weekly injection of PEG-IFN facilitates a longer duration of treatment which may be critical for benefit. We thus compared adjuvant therapy of flat low-dose PEG-IFN (36 months) versus low-dose IFN (18 months) in intermediate-risk M pts without macro-metastatic nodes. Methods: In this multicenter, open-label, prospective randomized phase III trial, pts with resected M ≥ 1.5 mm in thickness and without clinically detectable nodes were randomized either to IFN (3 MU subcutaneously [sc] 3 times a week for 18 months) or to PEG-IFN (100 mcg sc once weekly for 36 months). Sentinel node procedure (SNP) was not a standard in 2003 and thus was optional. Approach was consistent by center. Randomization was stratified for centers and SNP procedure. Primary endpoint was relapse-free survival (RFS), and secondary were distant metastasis-free survival (DMFS), overall survival (OS), and grade 3-4 severe adverse events (SAE). Sample size (890 pts) was calculated to detect a 10% difference (power >80%, type I error of 5%, 2-sided) for RFS. Analysis describes 5-year probability of survival. Comparisons were done by intent-to-treat using Cox proportional models. Results: Of 898 pts enrolled, 896 (443 PEG vs 453 IFN) were eligible for evaluation after a median follow-up of 4.7 years. SLNB was performed in 68.2% of pts. Neither RFS (PEG-IFN 66.2% vs IFN 64.8%, p=0.43; HR, 0.91; 95% CI, 0.73 to 1.15) nor DMFS (71.3% vs 72.6%, p=0.86; HR, 1.02; 95% CI, 0.80 to 1.32) or OS (77.0% vs 78.4%, p=0.55; HR, 1.09; 95% CI, 0.82 to 1.45) showed statistical difference. There was an excess of SAE grade 3-4 in PEG-IFN arm (44.6% vs 26.6% in the first 18 months) which impacted on median duration of treatment (17.8 months in IFN arm; 19.2 in PEG-IFN arm, with only 28% completing 36 months treatment). Conclusions: Flat low-dose PEG-IFN did not show superiority over conventional low dose IFN. Attempts to increase benefit by prolonging treatment with PEG-IFN over 3 years were hampered by a high rate of treatment discontinuation possibly linked to SAEs with PEG-IFN. [Table: see text]

Adjuvant chemotherapy with S-1 after curative treatment in patients with head and neck cancer (ACTS-HNC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6004-6004 ◽  
Author(s):  
Takahide Taguchi ◽  
Akira Kubota ◽  
Kunitoshi Yoshino ◽  
Kichinobu Tomita ◽  
Naoyuki Kohno ◽  
...  
Keyword(s):  
Adjuvant Chemotherapy ◽  
Head And Neck ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Curative Treatment ◽  
Free Survival ◽  
End Point ◽  
Phase Iii Study ◽  
P 16 ◽  
Grade 3

6004 Background: To establish the efficacy of adjuvant chemotherapy with S-1 (tegafur gimeracil oteracil potassium) after curative treatment in patients with advanced squamous cell carcinoma of the head and neck (SCCHN), we conducted a randomized phase III study to investigate whether S-1 is superior to UFT (uracil/tegafur). Methods: Patients with SCCHN who had received curative treatment and were confirmed to be tumor-free were randomly assigned to receive UFT (300 or 400 mg/day for 1 year) or S-1 (80, 100, or 120 mg/day for 1 year). The primary end point was disease-free survival (DFS). Secondary end points were overall survival (OS), relapse-free survival (RFS), and safety. We estimated that 500 patients were needed to establish the primary end point. Results: From April 2006 through November 2008, a total of 526 patients (262 assigned to UFT; 264 assigned to S-1) were enrolled. The 3-year DFS rate was 66.0% in the UFT group and 64.1% in the S-1 group (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.66 to 1.16; [log-rank], P = .34). The 3-year OS rate was 75% in the UFT group and 82.9% in the S-1 group (HR, 0.64; 95% CI, 0.44 to 0.94; [log-rank], P = .022). The 3-year RFS rate was 63.6% in the UFT group and 68.2% in the S-1 group (HR, 0.81; 95% CI, 0.60 to 1.09; [log-rank], P = .16). There were no significant differences in 3-year DFS or RFS; however, the 3-year OS was significantly better in the S-1 group. The incidence of the following grade 3 or 4 events was significantly higher in the S-1 group: oral mucositis/stomatitis (2.4%), leukopenia (5.2%), neutropenia (3.6%), and thrombocytopenia (5.0%). Conclusions: S-1 was not demonstrated to be superior to UFT in terms of 3-year DFS; however, 3-year OS was significantly better with S-1 than with UFT. Clinical trial information: NCT00336947.

scholarly journals Intensive Chemotherapy Along with Aggressive Supportive Care Can Spare Stem Cell Transplantation in a Subset of Patients without Compromising an Outcome in Infants with Acute Lymphoblastic Leukemia; A Report from the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) Trial MLL-10

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2626-2626
Author(s):  
Daisuke Tomizawa ◽  
Takako Miyamura ◽  
Toshihiko Imamura ◽  
Tomoyuki Watanabe ◽  
Akiko Moriya Saito ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Supportive Care ◽  
Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Intensive Chemotherapy ◽  
Free Survival ◽  
Cns Disease

BACKGROUND: Outcome of infants with acute lymphoblastic leukemia (ALL), especially those with rearrangement of MLL (KMT2A) gene (MLL-r), is extremely poor. A strategy to perform allogeneic hematopoietic stem cell transplantation (HSCT) for all the infants with MLL-r ALL in first remission (1CR) have been tested in the previous Japanese trials MLL96/98/03, however, the improvement was modest. Given the recent evidence of a limited role of HSCT especially in infants lacking poor prognostic factors, efficacy and safety of an intensive chemotherapy and risk stratification to limit HSCT for only infants with high-risk of relapse were evaluated in the JPLSG MLL-10 trial (UMIN000004801). PATIENTS & METHODS: Infants age less than 365 days with ALL were registered in the MLL-10 study and were stratified by their MLL gene status, age at diagnosis, and presence of CNS disease; low-risk (LR), if the patients had germline MLL gene (MLL-g); intermediate-risk (IR), if the patients with MLL-r ALL were age 180 days or older and lack CNS disease; high-risk (HR), if the patients with MLL-r ALL were age <180 days or having CNS disease. All the infants with MLL-r ALL received Interfant induction followed by COG AALL0631 post-remission chemotherapy with modification of adding high-dose cytarabine in early intensification phase. All the HR cases were allocated to HSCT in 1CR. LR cases were treated based on the Japanese MLL96/98 MLL-g chemotherapy. Minimal residual disease (MRD) was evaluated in 3 methods, flowcytometry, PCR of MLL fusion transcripts, and PCR targeting IgH/TCR rearrangements, but were not used to guide therapies. RESULTS: A total of 90 eligible infants with ALL were registered in the MLL-10 study between Jan/2011 and Dec/2014; 15 cases were stratified as LR, 19 as IR, and 56 as HR. Remission status was evaluated after 2 chemotherapy courses; 82 (91.1%) achieved 1CR, 3 failed to achieve 1CR, and 5 discontinued the trial before CR evaluation. No early death was observed. With median follow-up period of 1954 days (range, 534-2835 days) in the live patients, 3-year probability of event-free survival (pEFS) and overall survival (pOS) were 70.9% (95% CI, 60.0-79.3%) and 86.6% (77.6-92.2%), respectively. Among the MLL-r cases, 3-year pEFS and pOS were 66.2% (53.9-75.9%) and 83.9% (73.4-90.5%), respectively. According to the risk groups, 3-year pEFS were 93.3% (61.2-99.0%) for LR, 94.4% (66.6-99.2%) for IR, and 56.6% (42.4-68.6%) for HR cases. Regarding the MRD studies, correlation of MRD results in 3 methodologies seemed reasonable, but while flow-MRD could be evaluated in 85 cases, MLL-fusion PCR-MRD (MLL-r cases only) and IgH/TCR PCR-MRD could only be evaluated in 55 and 50 cases, respectively. In the univariable analysis for MLL-r cases, female sex (P=0.04), younger age at diagnosis (P=0.01), and 0.01%< flow-MRD after 2 courses of chemotherapy (P<0.01) had negative impact on pEFS. In multivariable analysis, female sex (P=0.01) and positive flow-MRD (P<0.01) were poor prognostic. Among the 38 HR cases who received HSCT in 1CR per protocol, 3-year probability of disease-free survival was 65.7% (48.3-78.4%) and only one non-relapse death was observed. CONCLUSIONS: Introduction of intensive chemotherapy enabled us to spare allogeneic HSCT in 1CR at least in a subset of infants with MLL-r ALL without compromising their outcome. This was accomplished also because of the aggressive supportive care provided to the study cases, such as full hospitalization during and after the intensive treatment phases, intensive use of rasburicase to prevent tumor lysis syndromes, and aggressive infection prophylaxis. However, outcome of HR MLL-r cases is still unsatisfactory, and introduction of novel agents is mandatory for further improvement in the outcome of infants with ALL. Figure Disclosures No relevant conflicts of interest to declare.

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