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P-Y Dumas,
A Ruggeri,
M Robin,
A Crotta,
J Abraham,
E Forcade,
J-O Bay, M Michallet,
Y Bertrand,
G Socié,
I Ionescu,
E Gluckman,
N Milpied,
V Rocha
[show abstract]
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ABSTRACT: EBV viremia and post-transplantation lymphoproliferative disorders (PTLDs) have been associated with high mortality rates after allogeneic hematopoietic SCT (allo-HSCT). Few retrospective studies, without EBV load monitoring postulated that umbilical cord blood transplantation (UCBT) might be associated with high incidence of EBV events. We retrospectively studied 175 UCBT recipients for whom RQ-PCR was used to monitor EBV blood load at least once a week during the first 3 months after UCBT. Median age was 23 years, 74% had leukemia. Conditioning was myeloablative in 54% and reduced intensity conditioning (RIC) was used in 46%. A total of 24 patients presented an EBV reactivation. For 15 patients, the reactivation occurred during the first 100 days (cumulative incidence: 8%) and included 4 EBV-PTLD. Rituximab as preemptive treatment was used in 12 of these 15 patients. In univariate analysis, the increased risk of early EBV reactivation was associated with RIC in combination with antithymocyte globulin (P=0.03) and previous history of auto-HSCT (P=0.01). Multivariate analysis did not find any independent risk factor. EBV reactivation as time-dependent covariate was not statistically associated with survival. Therefore, EBV events were not major complications after UCBT when EBV load is weekly monitored and preemptive treatment started.Bone Marrow Transplantation advance online publication, 9 July 2012; doi:10.1038/bmt.2012.117.
Bone marrow transplantation 07/2012; · 3.00 Impact Factor
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N Dhédin,
T Prébet,
R Peffault De Latour,
S Katsahian,
M Kuentz,
N Piard,
D Réa,
F Norol,
J P Jouet,
J A Ribeil,
R Tabrizi,
B Rio,
B Lioure,
P Tiberghien,
J H Bourhis,
A Sirvent,
P Bordigoni,
D Blaise, M Michallet,
J P Vernant
[show abstract]
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ABSTRACT: The correlation between the incidence of GVHD and the number of infused CD34(+) cells remains controversial for PBSC transplantation after a reduced-intensity-conditioning (RIC) regimen. We evaluated 99 patients transplanted with an HLA-identical sibling after the same RIC (2-Gy-TBI/fludarabine). Donor and recipient characteristics, donor's blood G-CSF-mobilized CD34(+) cell count, and number of infused CD34(+) and CD3(+) cells were analyzed as risk factors for acute and chronic GVHD There was a trend for an increased incidence of extensive chronic GVHD in the quartile of patients receiving more than 10 × 10(6) CD34(+) cells/kg (P=0.05). Interestingly, the number of donor's blood CD34(+) cells at day 5 of G-CSF mobilization was closely associated with the incidence of extensive chronic GVHD, that is, 48% (95% CI: 28-68) at 24-months in the quartile of patients whose donors had the highest CD34(+) cell counts versus 24.3% (95% CI: 14-34) in the other patients (P=0.007). In multivariate analysis, the only factor correlating with extensive chronic GVHD (cGVHD) was the donor's blood CD34(+) cell count after G-CSF (HR 2.49; 95% CI: 1.16-5.35, P=0.019). This study shows that the incidence of cGVHD is more strongly associated with the donor's ability to mobilize CD34(+) cells than with the number of infused CD34(+) cells.Bone Marrow Transplantation advance online publication, 21 May 2012; doi:10.1038/bmt.2012.75.
Bone marrow transplantation 05/2012; · 3.00 Impact Factor
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A Xhaard,
F Lanternier,
R Porcher,
E Dannaoui,
A Bergeron,
L Clement,
C Lacroix,
R Herbrecht,
F Legrand,
M Mohty, M Michallet,
C Cordonnier,
S Malak,
D Guyotat,
Lj Couderc,
G Socié,
N Milpied,
O Lortholary,
P Ribaud
[show abstract]
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ABSTRACT: Clin Microbiol Infect 2012; 18: E396-E400 ABSTRACT: We conducted a nationwide retrospective study to evaluate clinical characteristics and outcome of mucormycosis among allogeneic haematopoietic stem cell transplant recipients. Twenty-nine patients were diagnosed between 2003 and 2008. Mucormycosis occurred at a median of 225 days after allogeneic haematopoietic stem cell transplant, and as a breakthrough infection in 23 cases. Twenty-six patients were receiving steroids, mainly for graft-versus-host disease treatment, while ten had experienced a prior post-transplant invasive fungal infection. Twenty-six patients received an antifungal treatment; surgery was performed in 12. Overall survival was 34% at 3 months and 17% at 1 year.
Clinical Microbiology and Infection 05/2012; 18(10):E396-E400. · 4.54 Impact Factor
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M A Hospital,
X Thomas,
S Castaigne,
E Raffoux,
C Pautas,
C Gardin,
J-H Bourhis,
O Reman,
T de Revel,
C Terré,
C Preudhomme,
P Fenaux, M Michallet,
G Socié,
H Dombret
[show abstract]
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ABSTRACT: To illustrate methodological issues, we compared donor vs no-donor to transplant vs no-transplant comparisons in a cohort of 107 patients aged 50 years with adverse karyotype AML in first CR. Adverse karyotypes were defined as -7, del(7q), -5, del(5q), t(9;22), 11q23, 3q26 or complex abnormalities. Mantel-Byar estimations and hematopoietic SCT (HSCT) as a time-dependent variable were used to compare transplant vs no-transplant cumulative incidence of relapse (CIR), relapse-free survival (RFS) and OS. In all, 52 patients had a sibling donor, but only 35 of them were transplanted in first CR, whereas 9 patients received HSCT from alternative stem cell sources. Donor-based analysis showed lower CIR in the donor group, not translating in prolonged RFS or OS. Conversely, transplant-based analysis showed that HSCT in the first CR improved the three CIR (multivariate hazard ratio (HR), 0.31; P<0.001), RFS (multivariate HR, 0.57; P=0.047) and OS (multivariate HR, 0.54; P=0.03) endpoints. At 5 years, OS was estimated at 33% in transplanted vs 18% in non-transplanted patients. The positive effect of HSCT was more pronounced in patients aged 35 years and/or in those transplanted in the more recent years. These results confirm that HSCT is likely the best curative option in younger patients with adverse karyotype AML.Bone Marrow Transplantation advance online publication, 19 March 2012; doi:10.1038/bmt.2012.49.
Bone marrow transplantation 03/2012; · 3.00 Impact Factor
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C Sebban,
A Lefranc,
L Perrier,
P Moreau,
D Espinouse,
A Schmidt,
L Kammoun,
H Ghesquieres,
C Ferlay,
J O Bay,
S Lissandre,
D Pérol, M Michallet,
P Quittet
[show abstract]
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ABSTRACT: To evaluate in a multicentre randomised study the effect on duration of febrile neutropenia (FN), the safety and cost-effectiveness of a single subcutaneous pegfilgrastim injection compared with daily injections of filgrastim after peripheral blood stem cell transplantation in patients receiving high dose chemotherapy for myeloma and lymphoma.
Patients were randomly assigned to a single dose of pegfilgrastim at day 5 (D5) or daily filgrastim from D5 to the recovery of absolute neutrophil count (ANC) to 0.5 G/L. Duration of FN, of neutrophil and platelet recovery, transfusion and antibiotic requirements were the main end-points of the study. Costs were calculated from D0 until transplant unit discharge. The incremental cost-effectiveness ratio was expressed as the cost per day of FN prevented. Probabilistic sensitivity analysis was performed by non-parametric bootstrap methods.
Between October 2008 and September 2009, 10 centres enrolled 151 patients: 80 patients with lymphoma and 71 patients with myeloma. The mean duration of FN was 3.07 days (standard deviation (SD) 1.96) in the pegfilgrastin arm and 3.29 (SD 2.54) in the filgrastim one. Mean total costs were 23,256 and 25,448 euros for pegfilgrastim and filgrastim patients, respectively. There was a 62% probability that pegfilgrastim strictly dominates filgrastim. CONCLUDING STATEMENT: Pegfilgrastim after PBSC transplantation in myeloma and lymphoma is safe, effective when compared with filgrastim and could represent a cost-effective alternative in this setting.
European journal of cancer (Oxford, England: 1990) 01/2012; 48(5):713-20. · 4.12 Impact Factor
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M Michallet,
T Bénet,
M Sobh,
S Kraghel,
M El Hamri,
G Cannas,
F E Nicolini,
H Labussière,
S Ducastelle,
F Barraco,
X Thomas,
Y Chelghoum,
M-C Nicolle,
A-L Bienvenu,
F Persat,
F De Monbrison,
S Picot,
P Vanhems
[show abstract]
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ABSTRACT: Invasive aspergillosis (IA) during induction chemotherapy of acute myeloid leukemia (AML) could worsen the prognosis. Our objective was to study how the development of IA during AML interferes with the therapeutic strategy and to evaluate its impact on the short- and long-term survival. Newly diagnosed AML patients between the years 2004 and 2007 were retrospectively analyzed. The outcome was death of the patient. A Cox proportional hazards model with the diagnosis of IA and post-induction response evaluation as the main exposure was fitted. Overall, 262 patients were analyzed and 58 IA were observed. The 2-year survival of patients having had remission of AML was 54% and, for patients with failure of chemotherapy, it was 5% (p < 0.001). The 2-year survival of patients having had IA was 14%, and without IA, it was 32% (p = 0.01). Multivariate analysis showed that IA was associated with a higher risk of death in case of remission compared to no IA (hazard ratio [HR] = 1.66 [1.05-2.65], p = 0.031) and also in case of failure (HR = 6.43, p < 0.001). IA was associated with an increased risk of death for patients if they were either in remission or in failure after induction chemotherapy.
European Journal of Clinical Microbiology 09/2011; 31(6):991-7. · 2.86 Impact Factor
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J O Bay,
A Cabrespine,
C Faucher,
R Tabrizi,
P Bordigoni,
A Berceanu,
V Coiteux,
M Renaud,
V Mialou,
M Robin, [......],
F Witz,
A Buzyn,
T De Revel,
C Galambrun,
E Deconinck,
N Contentin,
S François,
N Gratecos,
D Blaise, M Michallet
[show abstract]
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ABSTRACT: The purpose of this paper is to describe the outcome of patients who underwent double allogeneic hematopoietic stem cell transplantation (AHSCT) with reduced-intensity conditioning regimens (RIC). Forty-five patients who received double RIC-AHSCT between 1997 and 2006 were retrospectively studied. The predominant diagnosis was acute myeloid leukemia (AML) (n = 17). Other diagnoses were aplasic anemia (AA) (n = 5), myelodysplasic disorder (n = 5), acute lymphoblastic leukemia (ALL) (n = 4), chronic myelomonocytic leukemia (CML) (n = 3), myeloma (n = 3), non-Hodgkin lymphoma (NHL) (n = 3), chronic lymphocytic leukemia (CLL) (n = 2), Hodgkin's disease (HD) (n = 2), and chronic myelomonocytic leukemia (n = 1). Main indications for RIC-AHSCT 2 were relapse (n = 25, 56%) and early (n = 8, 18%) or late (n = 12, 26%) graft failure. Median delays to reach a neutrophil count of 0.5 × 10(9)/L and platelet counts of 50 × 10(9)/L were significantly smaller after the second AHSCT. Among 25 patients who relapsed after RIC-AHSCT 1, 14 patients (56%) presented a response improvement after RIC-AHSCT 2. In this group, 9 patients sustained a complete response and 5 patients a partial response. Moreover, among the 20 patients who had early or late graft failure following RIC-AHSCT 1, 9 (45%) finally reached an engraftment. Disease-free survival (DFS) was significantly improved after RIC-AHSCT 2. Thirteen patients (28%) died of transplant-related mortality (TRM) at a median delay of 69 days (range: 0-451) after RIC-AHSCT 2. Double RIC-AHSCT is a feasible procedure that allows a response or engraftment not observed after RIC-AHSCT 1. The main indication is relapse. However, TRM remains high.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 07/2011; 18(2):250-6. · 3.15 Impact Factor
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C Faucher,
A G Le Corroller Soriano,
B Esterni,
N Vey,
A M Stoppa,
C Chabannon,
M Mohty, M Michallet,
J O Bay,
D Genre,
D Maraninchi,
P Viens,
J P Moatti,
D Blaise
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ABSTRACT: We report the first randomized study comparing early hospital discharge with standard hospital-based follow-up after high-dose chemotherapy (HDCT) and PBSCT. Patients aged 18-65 years, with an indication of PBSCT for non-leukemic malignant diseases were randomly assigned between two arms. Arm A consisted of early hospital discharge (HDCT during hospitalization, discharge at day 0, home stay with a caregiver, outpatient clinic follow-up). In arm B patients were followed up as inpatients. In total 131 patients were analyzed (66 in arm A and 65 in arm B). Patient characteristics and hematological reconstitution were comparable between the two groups. In arm A, 26 patients were actually discharged early. Patients in group A spent fewer days in hospital (11 vs 12 days, P=0.006). This strategy resulted in a 6% mean cost reduction per patient when compared with the conventional hospital-based group. The early discharge approach within the French health system, while safe and feasible, is highly dependent on social criteria (caregiver availability and home to hospital distance). It is almost always associated with conventional hospital readmission during the aplasia phase, and limits cost savings when considering the whole population of patients benefiting from HDCT in routine clinical practice.
Bone marrow transplantation 07/2011; 47(4):549-55. · 3.00 Impact Factor
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[show abstract]
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ABSTRACT: Acute myeloblastic leukaemia (AML) patients are at high risk of suffering from invasive fungal infections (IFI). Posaconazole demonstrated higher efficacy than standard azole agents (SAA) in the prophylaxis of IFI in this population. The authors estimated the cost effectiveness of posaconazole versus SAA in France.
A decision-tree model was developed to compare posaconazole with SAA with the results of a published clinical trial. Clinical events were modelled with chance nodes reflecting probabilities of IFI, IFI-related death, and death from other causes. Medical resource consumption and costs were obtained from results of the clinical trial and from a dedicated survey on the costs of treating IFI using a retrospective chart review design.
IFI treatment costs were estimated using medical files from 50 AML patients from six French centres, with a proven and probable IFI, who had been followed-up for 298 days on average. Direct costs directly related to IFI were estimated at €51,033, including extra costs of index hospitalisation, costs of antifungal therapy and additional hospitalisations related to IFI treatment. The model indicated that the healthcare costs for the posaconazole strategy were €5,223 (€2,697 for prophylaxis and €2,526 for IFI management), which was €859 less than the €6,083 in costs with SAA (€469 for prophylaxis and €5614 for IFI management). A sensitivity analysis indicated that there was an 80% probability that prophylaxis using the posaconazole strategy would be superior.
The findings from this analysis suggest that posaconazole use is a clinically and economically dominant strategy in the prophylaxis of IFI in AML patients, given the usual limits of economic models and the uncertainty of costs estimates.
Journal of Medical Economics 01/2011; 14(1):28-35.
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R Crocchiolo,
F-E Nicolini,
M Sobh,
S Ducastelle-Lepretre,
H Labussiere,
V Dubois,
C Auxenfans,
A Mojallal,
O Damour,
F Braye, M Michallet
Bone marrow transplantation 11/2010; 46(8):1153-5. · 3.00 Impact Factor
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M Michallet,
M Sobh,
D Milligan,
S Morisset,
D Niederwieser,
V Koza,
T Ruutu,
N H Russell,
L Verdonck,
N Dhedin,
A Vitek,
M Boogaerts,
L Vindelov,
J Finke,
V Dubois,
A van Biezen,
R Brand,
T de Witte,
P Dreger
[show abstract]
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ABSTRACT: We analyzed 368 chronic lymphocytic leukemia patients who underwent allogeneic hematopoietic stem cell transplantation reported to the EBMT registry between 1995 and 2007. There were 198 human leukocyte antigen (HLA)-identical siblings; among unrelated transplants, 31 were well matched in high resolution ('well matched' unrelated donor, WMUD), and 139 were mismatched (MM), including 30 matched in low resolution; 266 patients (72%) received reduced-intensity conditioning and 102 (28%) received standard. According to the EBMT risk score, 11% were in scores 1-3, 23% in score 4, 40% in score 5, 22% in score 6 and 4% in score 7. There was no difference in overall survival (OS) at 5 years between HLA-identical siblings (55% (48-64)) and WMUD (59% (41-84)), P=0.82. In contrast, OS was significantly worse for MM (37% (29-48) P=0.005) due to a significant excess of transplant-related mortality. Also OS worsened significantly when EBMT risk score increased. HLA matching had no significant impact on relapse (siblings: 24% (21-27); WMUD: 35% (26-44), P=0.11 and MM: 21% (18-24), P=0.81); alemtuzumab T-cell depletion and stem cell source (peripheral blood) were associated with an increased risk. Our findings support the use of WMUD as equivalent alternative to HLA-matched sibling donors for allogeneic HSCT in CLL, and justify the application of EBMT risk score in this disease.
Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 10/2010; 24(10):1725-31. · 8.30 Impact Factor
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[show abstract]
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ABSTRACT: Chimerism analysis after allogeneic haematopoietic stem cell transplantation has been used to document engraftment and to adapt therapy promptly. The aim of this study was to document engraftment and to detect as soon as possible relapse in patients with acute myeloid leukaemia who underwent stem cell transplantation. Real-time quantitative polymerase chain reaction is a highly sensitive and reproducible technology. It is useful in some disease to target selected sub-populations in order to have an earlier detection of relapse on cell fractions. In the acute myeloid leukaemia (n=65), analysis of the chimerism on whole peripheral blood cells and bone marrow cells, CD3+ cells, specific myeloid CD33+ cells (from blood) and CD34+ cells (from bone marrow) is of importance. After transplant, 25 patients relapsed (38%), three massively, with chimerism detection in whole blood and bone marrow and 22 insidiously following two different schemes (GRI and GRII). In GRI, (n=13): chimerism of CD33+ and CD34+ cellular fractions allowed an early detection of relapse in 100% of cases undetected in whole cells whereas in GRII (n=9): myeloid cells could identified relapse in 89% of cases when whole blood cells and CD3+ cells expressed a mixed chimerism. This study highlighted the importance of sub-cellular population chimerism documentation enable to ascertain a stable engraftment and to detect early relapse. The selection of sub-cellular population studied with high sensitive technology allows a rapid and efficient intervention before the onset of clinical signs in patient with acute myeloid leukaemia and could improve the patient's follow-up.
Pathologie Biologie 09/2010; 60(2):106-11. · 1.53 Impact Factor
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M Mohty,
M Labopin,
M L Balère,
G Socié,
N Milpied,
R Tabrizi,
N Ifrah,
Y Hicheri,
N Dhedin, M Michallet,
A Buzyn,
J-Y Cahn,
J-H Bourhis,
D Blaise,
C Raffoux,
H Espérou,
I Yakoub-Agha
[show abstract]
[hide abstract]
ABSTRACT: This retrospective report assessed the impact of rabbit antithymocyte globulins (ATG), incorporated within a standard myeloablative conditioning regimen prior to allogeneic stem cell transplantation (allo-SCT) using human leukocyte antigen-matched unrelated donors (HLA-MUD), on the incidence of acute and chronic graft-vs-host disease (GVHD). In this series of leukemia patients, 120 patients (70%) did not receive ATG ('no-ATG' group), whereas 51 patients received ATG ('ATG' group). With a median follow-up of 30.3 months, the cumulative incidence of grade 3-4 acute GVHD was 36% in the no-ATG group and 20% in the ATG group (P = 0.11). The cumulative incidence of extensive chronic GVHD was significantly lower in the ATG group as compared to the no-ATG group (4 vs 32%, respectively; P = 0.0017). In multivariate analysis, the absence of use of ATG was the strongest parameter associated with an increased risk of extensive chronic GVHD (relative risk) = 7.14, 95% CI: 1.7-33.3, P = 0.008). At 2 years, the probability of nonrelapse mortality, relapse, overall and leukemia-free survivals was not significantly different between the no-ATG and ATG groups. We conclude that the addition of ATG to GVHD prophylaxis resulted in decreased incidence of extensive chronic GVHD without an increase in relapse or nonrelapse mortality, and without compromising survival after myeloablative allo-SCT from HLA-MUD.
Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 09/2010; 24(11):1867-74. · 8.30 Impact Factor
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P Moreau,
C Hulin,
G Marit,
D Caillot,
T Facon,
P Lenain,
C Berthou,
B Pégourié,
A M Stoppa,
P Casassus, M Michallet,
L Benboubker,
H Maisonneuve,
C Doyen,
S Leyvraz,
C Mathiot,
H Avet-Loiseau,
M Attal,
J L Harousseau
Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 06/2010; 24(6):1233-5. · 8.30 Impact Factor
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M. Michallet,
B. Corront,
L. Molina,
A. Gratwohl,
N. Milpied,
C. Dauriac,
S. Brunet,
J. Soler,
J. P. Jouet,
H. Esperou Bourdeau,
W. Arcese,
F. Witz,
A. Moine,
F. E. Zwaan
[show abstract]
[hide abstract]
ABSTRACT: Allogeneic bone marrow transplantation (BMT) was performed in 17 patients with chronic lymphocytic leukemia (CLL): 15 resistant and 2 untreated forms; 12 males and 5 females with a mean age of 40 years (32–49). The conditioning regimen and graft versus host disease (GVHD) prophylaxis were varied. Successful engraftment was obtained in 15 evaluable cases. Lymphocytosis and clinical symptoms subsided in all but one case. All 15 evaluable patients developed acute GVHD. Among the 17 patients grafted, one early death was observed at the 15th day post-BMT, and one refractory form died 2 months after BMT. Of the remaining 15 patients in complete remission (CR0, 4 died from GVHD, hemorrhage, and graft failure, and 2 relapsed at 7 and 54 months after BMT and died. 9 patients are alive in CR with a mean follow-up of 25.6 months (4–48). Chimerism was complete in 8 patients and partial in the 2 T-depleted cases. In one case, an immunoglobulin gene rearrangement study was performed showing no residual disease. These results suggest that allogeneic BMT might be proposed as an alternative and possibly curative therapy for refractory CLL in young patients when performed earlier in the disease course.
06/2009; 5(s1):127-131.
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Bone Marrow Transplantation 07/2008; 41(12):1059-61. · 3.75 Impact Factor
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British Journal of Haematology 03/2008; 60(4):770 - 770. · 4.94 Impact Factor
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Leukemia 11/2007; 21(10):2204-6. · 9.56 Impact Factor
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P Moreau,
M Attal,
F Garban,
C Hulin,
T Facon,
G Marit, M Michallet,
C Doyen,
S Leyvraz,
M Mohty, [......],
J Jaubert,
T Lamy,
P Casassus,
M Dib,
B Kolb,
V Dorvaux,
B Grosbois,
I Yakoub-Agha,
J L Harousseau,
H Avet-Loiseau
[show abstract]
[hide abstract]
ABSTRACT: One hundred de novo multiple myeloma patients with t(4;14) treated with double intensive therapy according to IFM99 protocols were retrospectively analyzed. The median overall survival (OS) and event-free survival (EFS) were 41.4 and 21 months, respectively, as compared to 65 and 37 for patients included in the IFM99 trials without t(4;14) (P<10(-7)). We identified a subgroup of patients presenting at diagnosis with both low beta(2)-microglobulin <4 mg/l and high hemoglobin (Hb) >/=10 g/l (46% of the cases) with a median OS of 54.6 months and a median EFS of 26 months, respectively, which benefits from high-dose therapy (HDT); conversely patients with one or both adverse prognostic factor (high beta(2)-microglobulin and/or low Hb) had a poor outcome. The achievement of either complete response or very good partial response after HDT was also a powerful independent prognostic factor for both OS and EFS.
Leukemia 10/2007; 21(9):2020-4. · 9.56 Impact Factor
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X Thomas,
E Raffoux,
S de Botton,
C Pautas,
P Arnaud,
T de Revel,
O Reman,
C Terré,
B Corront,
C Gardin,
Q-H Le,
B Quesnel,
C Cordonnier,
J-H Bourhis,
M Elhamri,
P Fenaux,
C Preudhomme, M Michallet,
S Castaigne,
H Dombret
[show abstract]
[hide abstract]
ABSTRACT: In a multicenter trial, 259 young adults (15-49 years) with newly diagnosed acute myeloid leukemia (AML) were first randomized to receive a timed-sequential induction regimen given either alone (135 patients) or concomitantly with granulocyte-macrophage colony-stimulating factor (GM-CSF) (124 patients). Patients reaching complete remission (CR) were then randomized to compare a timed-sequential consolidation to a postremission chemotherapy including four cycles of high-dose cytarabine followed by maintenance courses. In the appropriate arm, GM-CSF was given concurrently with chemotherapy during all cycles of consolidation. CR rates were significantly better in the GM-CSF arm (88 vs 78%, P<0.04), but did not differ after salvage. Patients receiving GM-CSF had a higher 3-year event-free survival (EFS) estimate (42 vs 34%), but GM-CSF did not impact on overall survival. Patients with intermediate-risk cytogenetics benefited more from GM-CSF therapy (P=0.05) in terms of EFS than patients with other cytogenetics. This was also confirmed when considering only patients following the second randomization, or subgroups defined by a prognostic index based on cytogenetics and the number of courses required for achieving CR. Priming of leukemic cells with hematopoietic growth factors is a means of enhancing the efficacy of chemotherapy in younger adults with AML.
Leukemia 04/2007; 21(3):453-61. · 9.56 Impact Factor
