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1.
J Clin Oncol ; 35(4): 387-393, 2017 Feb.
Article in English | MEDLINE | ID: mdl-28129526

ABSTRACT

Purpose Elderly patients with acute myeloid leukemia (AML) have a poor prognosis, and innovative maintenance therapy could improve their outcomes. Androgens, used in the treatment of aplastic anemia, have been reported to block proliferation of and initiate differentiation in AML cells. We report the results of a multicenter, phase III, randomized open-label trial exploring the benefit of adding androgens to maintenance therapy in patients 60 years of age or older. Patients and Methods A total of 330 patients with AML de novo or secondary to chemotherapy or radiotherapy were enrolled in the study. Induction therapy included idarubicin 8 mg/m2 on days 1 to 5, cytarabine 100 mg/m2 on days 1 to 7, and lomustine 200 mg/m2 on day 1. Patients in complete remission or partial remission received six reinduction courses, alternating idarubicin 8 mg/m2 on day 1, cytarabine 100 mg/m2 on days 1 to 5, and a regimen of methotrexate and mercaptopurine. Patients were randomly assigned to receive norethandrolone 10 or 20 mg/day, according to body weight, or no norethandrolone for a 2-year maintenance therapy regimen. The primary end point was disease-free survival by intention to treat. Secondary end points were event-free survival, overall survival, and safety. This trial was registered at www.ClinicalTrials.gov identifier NCT00700544. Results Random assignment allotted 165 patients to each arm; arm A received norethandrolone, and arm B did not receive norethandrolone. Complete remission or partial remission was achieved in 247 patients (76%). The Schoenfeld time-dependent model showed that norethandrolone significantly improved survival for patients still in remission at 1 year after induction. In arms A and B, respectively, 5-year disease-free survival was 31.2% and 16.2%, event-free survival was 21.5% and 12.9%, and overall survival was 26.3% and 17.2%. Norethandrolone improved outcomes irrelevant to all prognosis factors. Only patients with baseline leukocytes > 30 × 109/L did not benefit from norethandrolone. Conclusion This study demonstrates that maintenance therapy with norethandrolone significantly improves survival in elderly patients with AML without increasing toxicity.


Subject(s)
Androgens/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Leukemia, Myeloid, Acute/drug therapy , Age Factors , Aged , Female , Humans , Male , Middle Aged
2.
Blood ; 118(3): 679-85, 2011 Jul 21.
Article in English | MEDLINE | ID: mdl-21622650

ABSTRACT

The prognosis of acute myeloid leukemia (AML) is very poor in elderly patients, especially in those classically defined as having unfavorable cytogenetics. The recent monosomal karyotype (MK) entity, defined as 2 or more autosomal monosomies or combination of 1 monosomy with structural abnormalities, has been reported to be associated with a worse outcome than the traditional complex karyotype (CK). In this retrospective study of 186 AML patients older than 60 years, the prognostic influence of MK was used to further stratify elderly patients with unfavorable cytogenetics. CK was observed in 129 patients (69%), and 110 exhibited abnormalities according to the definition of MK (59%). MK(+) patients had a complete response rate significantly lower than MK(-) patients: 37% vs 64% (P = .0008), and their 2-year overall survival was also decreased at 7% vs 22% (P < .0001). In multivariate analysis, MK appeared as the major independent prognostic factor related to complete remission achievement (odds ratio = 2.3; 95% confidence interval, 1-5.4, P = .05) and survival (hazard ratio = 1.7; 95% confidence interval, 1.1-2.5, P = .008). In the subgroup of 129 CK(+) patients, survival was dramatically decreased for MK(+) patients (8% vs 28% at P = .03). These results demonstrate that MK is a major independent factor of very poor prognosis in elderly AML.


Subject(s)
Chromosome Aberrations/statistics & numerical data , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/mortality , Monosomy/genetics , Aged , Female , Genetic Predisposition to Disease/epidemiology , Genetic Predisposition to Disease/genetics , Humans , Incidence , Male , Middle Aged , Multivariate Analysis , Prognosis , Retrospective Studies , Risk Factors
3.
Blood ; 116(17): 3157-62, 2010 Oct 28.
Article in English | MEDLINE | ID: mdl-20479285

ABSTRACT

The stem cell source for autologous transplantation has shifted from bone marrow to peripheral blood (PB). We previously showed that relapse incidence in patients with acute myelocytic leukemia autografted in first remission (CR1) was greater with PB than bone marrow, and a poorer outcome was associated with a shorter CR1 to PB transplantation interval (≤ 80 days). Leukemic and normal progenitors are CD34(+) and can be concomitantly mobilized; we assessed whether an association exists between the infused CD34(+) cell dose and outcome. The infused CD34(+) cell doses were available for 772 patients autografted more than 80 days after CR1 and were categorized by percentiles. We selected the highest quintile (> 7.16 × 10(6)/kg) as the cutoff point. By multivariate analysis, relapse was more probable in patients who received the highest dose (hazard ratio = 1.48; 95% confidence interval, 1.12-1.95; P = .005), and leukemia-free survival was worse (hazard ratio = 0.72; 95% confidence interval, 0.55-0.93; P = .01). In conclusion, in patients autografted in first remission, relapse was higher and leukemia-free survival lower for those who received the highest CD34(+) PB doses.


Subject(s)
Antigens, CD34/adverse effects , Leukapheresis , Leukemia, Myeloid, Acute/prevention & control , Leukemia, Myeloid, Acute/therapy , Adolescent , Adult , Aged , Disease-Free Survival , Humans , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/drug therapy , Middle Aged , Multivariate Analysis , Prognosis , Recurrence , Remission Induction , Transplantation, Autologous , Young Adult
4.
J Clin Oncol ; 28(18): 3028-34, 2010 Jun 20.
Article in English | MEDLINE | ID: mdl-20479424

ABSTRACT

PURPOSE: No significant improvement in treatment outcome has been seen in elderly patients with acute myeloid leukemia (AML) over the past 20 years. This retrospective analysis investigated the prognostic factors for complete remission (CR) and survival in older patients with AML. PATIENTS AND METHODS: The study involved 847 patients older than 60 years enrolled onto three trials carried out in France between 1995 and 2005. Induction therapy consisted of idarubicin (8 mg/m(2), days 1 through 5) and cytarabine (100 mg/m(2), days 1 through 7; group I, 339 patients) or the same drugs plus lomustine (200 mg/m(2) orally on day 1; group II, 508 patients). Consolidation therapy consisted of anthracycline and cytarabine courses at lower doses, preceded or not by a first course of intermediate-dose cytarabine. RESULTS: The rate of CR was significantly higher in patients in group II compared with group I (68% v 58%; P = .002). The rate of toxic death was similar in the two groups. In multivariate analysis, two prognostic factors were linked to CR: nonadverse cytogenetic (P < .003) and addition of lomustine to induction chemotherapy (P = .002). Median overall survival was significantly improved in patients treated with lomustine (median and SE, 12.7 +/- 2.2 months v 8.7 +/- 2.7 months; P = .004). In multivariate analysis, five prognostic factors positively affected overall survival: addition of lomustine (P = .002), age < or = 69 years (P < .001), Eastern Cooperative Oncology Group performance status lower than 2 (P = .002), French-American-British subgroup 1/2 (P = .02), and nonadverse cytogenetic (P < .001). CONCLUSION: Lomustine improves the rate of CR and survival in elderly patients with de novo AML when added to standard induction therapy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Leukemia, Myeloid, Acute/drug therapy , Aged , Aged, 80 and over , Cohort Studies , Cytarabine/administration & dosage , Female , Humans , Idarubicin/administration & dosage , Leukemia, Myeloid, Acute/mortality , Leukemia, Myeloid, Acute/pathology , Lomustine/administration & dosage , Male , Middle Aged , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Remission Induction , Retrospective Studies , Survival Rate , Treatment Outcome
5.
J Clin Oncol ; 27(28): 4747-53, 2009 Oct 01.
Article in English | MEDLINE | ID: mdl-19720919

ABSTRACT

PURPOSE: Acute myeloid leukemia (AML) with translocation (t) (8;21) or inversion (inv) (16) is associated with a favorable prognosis when treated with intensive chemotherapy. In elderly patients, these AML types are rare, and intensive treatments are much less tolerated. We conducted a retrospective study to evaluate the characteristics and outcome of AML with t(8;21) or inv(16) in the elderly. PATIENTS AND METHODS: Patients with t(8;21) or inv(16) AML who were age 60 years or older and who received at least one course of induction chemotherapy were included. Postremission therapy consisted of low-dose maintenance chemotherapy (n = 72) or intensive consolidation (n = 56). RESULTS: A total of 147 patients were analyzed. The median age was 67 years. Sixty patients had t(8;21), and 87 patients had inv(16). A total of 129 patients achieved complete response (CR) after one or two induction courses (ie, 88% CR rate), and 15 patients (10%) died early (ie, during the 8 weeks after induction). During a median follow-up of 48 months, the 5-year probabilities of overall survival (OS) and leukemia-free survival (LFS) were 31% and 27%, respectively. Multivariate analysis showed a negative impact of high WBC, impaired performance status, and deletion (9q) on OS and LFS. Administration of intensive consolidation was associated with better LFS only in patients with t(8;21). In addition, the need for critical care during induction independently predicted lower LFS. CONCLUSION: Because of a high CR rate, induction chemotherapy should be considered systematically for elderly patients who have AML with t(8;21) or inv(16). The high risk of relapse suggests that alternative strategies of postremission therapy are warranted.


Subject(s)
Chromosome Inversion , Chromosomes, Human, Pair 16/genetics , Chromosomes, Human, Pair 21/genetics , Chromosomes, Human, Pair 8/genetics , Leukemia, Myeloid/drug therapy , Translocation, Genetic , Acute Disease , Aged , Aged, 80 and over , Core Binding Factors/genetics , Female , Humans , Leukemia, Myeloid/genetics , Leukemia, Myeloid/pathology , Male , Middle Aged , Prognosis , Retrospective Studies , Survival Analysis , Treatment Outcome
6.
Blood ; 113(17): 3918-24, 2009 Apr 23.
Article in English | MEDLINE | ID: mdl-19109228

ABSTRACT

Many somatic genetic abnormalities have been identified in T-cell acute lymphoblastic leukemia (T-ALL) but each individual abnormality accounts for a small proportion of cases; therapeutic stratification consequently still relies on classical clinical markers. NOTCH1 and/or FBXW7 mutations both lead to activation of the NOTCH1 pathway and are among the most frequent mutations in T-ALL. We screened 141 adult diagnostic T-ALL samples from patients treated on either the Lymphoblastic Acute Leukemia in Adults (LALA)-94 (n = 87) or the GRAALL-2003 (n = 54) trials. In 88 cases (62%) there were demonstrated NOTCH1 mutations (42% heterodimerization [HD], 10% HD+proline glutamate serine threonine [PEST], 6% PEST, 2% juxtamembrane mutations, 2% transactivation domain [TAD]) and 34 cases (24%) had FBXW7 mutations (21 cases had both NOTCH1 and FBXW7 mutations); 40 cases (28%) were wild type for both. There was no significant correlation between NOTCH1 and/or FBXW7 mutations and clinico-biologic features. Median event-free survival (EFS) and overall survival (OS) were 36 versus 17 months (P = .01) and not reached versus 32 months (P = .004) in patients with NOTCH1 and/or FBXW7 mutations versus other patients, respectively. Multivariate analysis showed that the presence of NOTCH1/FBXW7 mutations was an independent good prognostic factor for EFS and OS (P = .02 and P = .01, respectively). These data demonstrate that NOTCH1 pathway activation by either NOTCH1 or FBXW7 mutation identifies a large group of patients with a favorable outcome that could justify individual therapeutic stratification for T-ALL.


Subject(s)
Cell Cycle Proteins/genetics , F-Box Proteins/genetics , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/classification , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Receptor, Notch1/genetics , Ubiquitin-Protein Ligases/genetics , Adult , Cell Cycle Proteins/metabolism , F-Box Proteins/metabolism , F-Box-WD Repeat-Containing Protein 7 , Genotype , Humans , Mutation/genetics , Phenotype , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/pathology , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/therapy , Prognosis , Receptor, Notch1/metabolism , Societies, Medical , Survival Rate , Time Factors , Treatment Outcome , Ubiquitin-Protein Ligases/metabolism
7.
J Clin Oncol ; 26(15): 2512-8, 2008 May 20.
Article in English | MEDLINE | ID: mdl-18413641

ABSTRACT

PURPOSE: The prognosis of relapsing primary CNS lymphoma (PCNSL) is poor. We report the results of a prospective multicenter trial of intensive chemotherapy followed by autologous hematopoietic stem-cell rescue (IC + HCR) in immunocompetent adult patients with PCNSL or intraocular lymphoma (IOL) after failure of high-dose methotrexate-based treatment. PATIENTS AND METHODS: Salvage treatment consisted of two cycles of high-dose cytarabine and etoposide (CYVE). Intensive chemotherapy combined thiotepa, busulfan, and cyclophosphamide. Forty-three patients (median age, 52 years; range, 23 to 65 years) were included, with relapse (n = 22), refractory disease (n = 17), or a partial response to first-line treatment (n = 4). The response to CYVE was not assessable in three cases because of treatment-related death. Twenty patients (47%) were chemosensitive to CYVE: 15 of them proceeded to IC + HCR. IC + HCR was also administered to 12 patients who did not respond to CYVE. All but one of the 27 patients who underwent IC + HCR entered complete remission. RESULTS: With a median follow-up of 36 months, the median overall survival was 18.3 months in the overall population, and 58.6 months among patients who completed IC + HCR. The respective median progression-free survival (PFS) times after IC + HCR were 11.6 and 41.1 months. The 2-year overall survival probability was 45% in the whole population and 69% among the 27 patients who received IC + HCR. The 2-year PFS probability was 43% among all the patients and 58% in the IC + HCR subpopulation. CONCLUSION: IC + HCR is an effective treatment for refractory and recurrent PCNSL.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Brain Neoplasms/therapy , Eye Neoplasms/therapy , Hematopoietic Stem Cell Transplantation , Lymphoma, Large B-Cell, Diffuse/therapy , Neoplasm Recurrence, Local/therapy , Salvage Therapy , Adult , Aged , Brain Neoplasms/drug therapy , Busulfan/administration & dosage , Combined Modality Therapy , Cyclophosphamide/administration & dosage , Cytarabine/administration & dosage , Etoposide/administration & dosage , Eye Neoplasms/drug therapy , Female , Humans , Lymphoma, Large B-Cell, Diffuse/drug therapy , Male , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Prospective Studies , Survival Rate , Thiotepa/administration & dosage
8.
Blood ; 110(3): 1025-8, 2007 Aug 01.
Article in English | MEDLINE | ID: mdl-17426258

ABSTRACT

The phosphoinositide 3-kinase (PI3K/Akt) pathway is activated in acute myelogenous leukemia (AML) and is promising for targeted inhibition. Ninety-two patients with primary AML were analyzed for PI3K/Akt constitutive activation. Fifty percent of the patients presented with constitutive PI3K activation (PI3K (+)). No difference was observed between PI3K (+) and PI3K (-) groups concerning age, sex, white blood cell count, lactate dehydrogenase (LDH) level, bone marrow blast cells, French-American-British (FAB) classification, cytogenetics, RAS or nucleophosmin (NPM) mutations. Slightly more FLT3-ITD was detected in the PI3K (-) group (P = .048). The complete remission rate was similar between the 2 groups. With a median follow-up of 26 months, we observed for PI3K (+) and PI3K (-) patients, respectively, 56% and 33% overall survival (P = .001) and 72% and 41% relapse-free survival (P = .001). Constitutive PI3K/Akt activity is a favorable prognosis factor in AML, even after adjustment for FLT3-ITD, and may confer a particular sensitivity to chemotherapy. A better understanding of the downstream effectors of the PI3K/Akt pathway is needed before targeting in AML.


Subject(s)
Blast Crisis/enzymology , Leukemia, Myeloid, Acute/enzymology , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Blast Crisis/drug therapy , Blast Crisis/genetics , Blast Crisis/mortality , Bone Marrow/enzymology , Bone Marrow/pathology , Disease-Free Survival , Enzyme Activation/genetics , Female , Humans , L-Lactate Dehydrogenase/genetics , L-Lactate Dehydrogenase/metabolism , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/mortality , Leukocyte Count , Male , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Nucleophosmin , Phosphatidylinositol 3-Kinases/genetics , Proto-Oncogene Proteins c-akt/genetics , Survival Rate , fms-Like Tyrosine Kinase 3/genetics , fms-Like Tyrosine Kinase 3/metabolism , ras Proteins/genetics , ras Proteins/metabolism
9.
Blood ; 109(4): 1408-13, 2007 Feb 15.
Article in English | MEDLINE | ID: mdl-17062730

ABSTRACT

The combination of imatinib with chemotherapy has been recently reported as very promising in patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). During 2004 and 2005, 45 patients with newly diagnosed Ph+ ALL were treated in the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAAPH) 2003 study, in which imatinib was started with HAM (mitoxantrone with intermediate-dose cytarabine) consolidation in good early responders (corticosensitive and chemosensitive ALL) or earlier during the induction course in combination with dexamethasone and vincristine in poor early responders (corticoresistant and/or chemoresistant ALL). Imatinib was then continuously administered until stem cell transplantation (SCT). Overall, complete remission (CR) and BCR-ABL real-time quantitative polymerase chain reaction (RQ-PCR) negativity rates were 96% and 29%, respectively. All of the 22 CR patients (100%) with a donor actually received allogeneic SCT in first CR. At 18 months, the estimated cumulative incidence of relapse, disease-free survival, and overall survival were 30%, 51%, and 65%, respectively. These 3 end points compared very favorably with results obtained in the pre-imatinib LALA-94 trial. This study confirms the value of the combined approach and encourages prospective trials to define the optimal chemotherapy that has to be combined with imatinib and to carefully reevaluate the place of allogeneic SCT in this new context.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Philadelphia Chromosome , Piperazines/administration & dosage , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Pyrimidines/administration & dosage , Adolescent , Adult , Benzamides , Cytarabine/therapeutic use , Female , Hematopoietic Stem Cell Transplantation , Humans , Imatinib Mesylate , Male , Middle Aged , Mitoxantrone/therapeutic use , Neoplasm, Residual , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Remission Induction , Survival Analysis , Transplantation, Homologous
10.
Br J Haematol ; 135(3): 382-5, 2006 Nov.
Article in English | MEDLINE | ID: mdl-16984386

ABSTRACT

In a phase II study, daclizumab was given as single second-line agent to 62 patients with steroid-refractory acute graft-versus-host disease (aGVHD). Complete resolution of aGVHD was achieved in 68.8% of patients. This response rate was significantly associated with a lower number of involved organs and smaller extent of skin involvement. The 4-year event-free survival (EFS) was 54.6%. Grade > or =III aGVHD, > or =2 involved organs at baseline and patient age >18 years were independently associated with lower EFS. Daclizumab could be a suitable alternative treatment for aGVHD, particularly when limited to the skin or gastrointestinal tract.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Graft vs Host Disease/drug therapy , Immunoglobulin G/therapeutic use , Immunosuppressive Agents/therapeutic use , Acute Disease , Adolescent , Adult , Age Factors , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal, Humanized , Child , Child, Preschool , Daclizumab , Female , Graft vs Host Disease/mortality , Graft vs Host Disease/pathology , Humans , Immunoglobulin G/adverse effects , Immunosuppressive Agents/adverse effects , Infant , Male , Middle Aged , Prospective Studies , Remission Induction , Stem Cell Transplantation/adverse effects , Survival Analysis , Treatment Outcome
11.
Biol Blood Marrow Transplant ; 11(6): 448-54, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15931633

ABSTRACT

To improve the results in the treatment of adult acute lymphoblastic leukemia patients, different strategies have been proposed. The intensification could concern the induction and early consolidation phases, the conditioning regimen before allogeneic bone marrow transplantation (alloBMT), or both. We analyzed 2 consecutive trials for adult patients in first remission and with the same prognostic features. The Leucemie Aigue Lymphoblastique Paris-Ouest-France (LALPOF) protocol proposed alloBMT with standard conditioning after a classic induction and intensified consolidation scheme; the Groupe Ouest Est des Leucemies Aigues Lymphoblastiques (GOLEAL1) protocol tested an intensified induction and consolidation course before alloBMT with a reinforced conditioning regimen. The 4-year survival rates after alloBMT for LALPOF and GOELAL1 were, respectively, 71% +/- 12% and 36% +/- 13% ( P = .009). The 4-year disease-free survival reached 75% +/- 11% in the LALPOF study and 69% +/- 13% in the GOELAL1 study ( P = .30). The toxic death rate was significantly lower in the LALPOF (2/18) than in the GOELAL1 (6/15) group. Event-free survival at 4 years was significantly higher in LALPOF than in GOELAL1: 66% +/- 11% and 35% +/- 11%, respectively ( P = .02). For adult acute lymphoblastic leukemia patients in first remission, the intensification of chemotherapy before a reinforced conditioning regimen before alloBMT may lead to an increased toxic death rate.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Bone Marrow Transplantation , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Transplantation Conditioning , Adolescent , Adult , Bone Marrow Transplantation/mortality , Female , Humans , Male , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Randomized Controlled Trials as Topic , Survival Analysis , Transplantation Conditioning/methods , Transplantation Conditioning/mortality , Transplantation, Homologous
12.
Blood ; 104(10): 3028-37, 2004 Nov 15.
Article in English | MEDLINE | ID: mdl-15256423

ABSTRACT

Various transplantation strategies have been designed to improve the poor prognosis of adult (ages 15 to 60 years) acute lymphoblastic leukemia (ALL). The GOELAL02 trial evaluated the impact of early allogeneic bone marrow transplantation (alloBMT) or delayed unpurged autologous stem cell transplantation (ASCT) for patients who had no human leukocyte antigen (HLA)-matched sibling donor or who were older than 50 years. Inclusion criteria included at least one of the following: age older than 35 years; non-T-ALL; leukocytosis greater than 30 x 10(9)/L; t(9;22), t(4;11), or t(1; 19); or failure to achieve complete remission (CR) after one induction course. Among 198 patients, the median age was 33 years. The CR rate was 80% with vincristine, idarubicine, L-asparaginase, and randomized intravenous injection or oral steroids (P = nonsignificant [ns]). AlloBMT was performed after 2 consolidation courses while ASCT was delayed after 1 additional reinduction. Intensified conditioning regimen before transplantation included etoposide, cyclophosphamide, and total body irradiation (TBI). Median follow-up was 5.1 years. The median overall survival (OS) was 29 months, with a 6-year OS of 41%. On an intent-to-treat analysis for patients younger than 50 years, alloBMT significantly improved the 6-year OS (75% versus 40% after ASCT; P = .0027). Randomized interferon-alpha maintenance had no effect on relapse or survival after ASCT. In conclusion, the outcome of adult ALL is better after early alloBMT than after delayed ASCT.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Bone Marrow Transplantation , Daunorubicin/analogs & derivatives , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Adolescent , Adult , Antineoplastic Agents/administration & dosage , Asparaginase/administration & dosage , Combined Modality Therapy , Daunorubicin/administration & dosage , Humans , Interferon-alpha/administration & dosage , Middle Aged , Philadelphia Chromosome , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Prognosis , Remission Induction , Transplantation, Homologous , Treatment Outcome , Vincristine/administration & dosage
13.
Eur J Haematol ; 71(5): 393-5, 2003 Nov.
Article in English | MEDLINE | ID: mdl-14667205

ABSTRACT

We report on a male patient affected by Shwachman Diamond syndrome (SDS) who presented an unusual delayed neutropenia and then developed a poorly differentiated acute myeloid leukaemia (M0-AML) with trilineage myelodysplasia in adulthood. Conventional cytogenetics revealed complex karyotypic changes (monosomies 20, 21, 22, additional 15p). The patient was treated with conventional chemotherapy but never reached complete remission of leukaemia and died 18 months after diagnosis. SDS is an inherited bone marrow failure syndrome with a high propensity to leukaemic transformation. Since neutropenia may be intermittent or with delayed onset, and leukaemic transformation may not occur until adulthood, full blood count should be regularly monitored in such patients.


Subject(s)
Exocrine Pancreatic Insufficiency/complications , Leukemia, Myeloid/etiology , Neutropenia/etiology , Acute Disease , Cell Differentiation , Child , Exocrine Pancreatic Insufficiency/genetics , Fatal Outcome , Genetic Predisposition to Disease , Humans , Leukemia, Myeloid/pathology , Male , Neutropenia/genetics , Pancytopenia/etiology , Sepsis/etiology , Syndrome
14.
Transfusion ; 43(7): 878-84, 2003 Jul.
Article in English | MEDLINE | ID: mdl-12823747

ABSTRACT

BACKGROUND: The implementation of a quality-assurance program is a major requirement to ensure quality and safety of the final PBPC components intended for clinical use. It is not clear whether the quantification of CFU-GM and CD34+ cells should be done on fresh components and after cryopreservation, which better represents the actual composition of the graft. STUDY DESIGN AND METHODS: Correlation between prefreeze and postthaw MNCs, CD34+ cells, and CFU-GM collected from 126 patients undergoing BMT (n=43) or PBPC (n =83) transplantation were evaluated. The statistical incidence of prefreeze and postthaw parameters as well as patient characteristics and conditioning regimens on hematologic recovery were analyzed. RESULTS: By multivariate analysis, prefreeze and postthaw CD34+ cells were the only two variables significantly and independently correlated to hematologic recovery. Low prefreeze and postthaw CD34+ cell numbers associated to a low CD34+ yield characterize PBPC grafts from patients who have the slowest hematologic recovery. The postthaw PBPC CD34+ cell number can be estimated before conditioning regimen by thawing a small aliquot of the graft. CONCLUSION: In association to prefreeze CD34+ cell number and to CD34+ yield, postthaw CD34+ cell number may be useful in monitoring cell loss during processing and identifying patients at risk of slow PBPC engraftment.


Subject(s)
Antigens, CD34/analysis , Cell Count , Cryopreservation , Hematopoietic Stem Cells/cytology , Peripheral Blood Stem Cell Transplantation , Adult , Blood Platelets/cytology , Bone Marrow Transplantation , Female , Flow Cytometry , Graft Survival , Granulocytes/cytology , Hematopoiesis , Hot Temperature , Humans , Male , Platelet Transfusion , Transplantation, Autologous , Treatment Outcome
15.
Blood ; 102(2): 462-9, 2003 Jul 15.
Article in English | MEDLINE | ID: mdl-12649129

ABSTRACT

Acute myeloid leukemias (AMLs) carrying inv(16)/t(16;16) chromosomal abnormalities are associated with a good prognosis. However, studies of this AML subtype have been hampered by the few number of patients reported, frequently collectively considered with those with AML carrying the t(8;21) translocation. We performed a retrospective study in 110 patients with inv(16)/t(16;16) AML (median age, 34 years) prospectively enrolled in 6 trials conducted in France between 1987 and 1998, with the aim to investigate prognostic factors for complete remission (CR) achievement and outcome of CR patients in this AML subtype. CR rate was 93%. Bad-prognosis factors for CR achievement were higher white blood cell count (WBC) and lower platelet count (optimal cutpoints at 120 and 30 x 109/L, respectively). At 3 years, estimated overall survival, disease-free survival (DFS), and cumulative incidence of relapse were 58%, 48%, and 42%, respectively. In multivariate analysis, (1) advanced age (optimal cutpoint, 35 years) was the only factor for shorter DFS and (2) advanced age and low platelet count were the 2 factors for shorter survival of CR patients. Outcome of CR patients (1) was not influenced by WBC and cytogenetic findings and (2) was similar among patients allocated to receive allogeneic transplantation, high-dose, or intermediate-dose cytarabine. Interestingly, advanced age was associated with a trend for more frequent additional chromosome abnormalities and predictive of higher cumulative incidence of relapse rather than death in first CR. These results markedly contrast with those reported in patients with t(8;21) AML in whom WBC, and not age, was the main high-risk factor for relapse, DFS, and survival.


Subject(s)
Chromosome Inversion , Chromosomes, Human, Pair 16/ultrastructure , Daunorubicin/analogs & derivatives , Leukemia, Myelomonocytic, Acute/mortality , Adolescent , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Child , Child, Preschool , Clinical Trials as Topic , Cytarabine/administration & dosage , Daunorubicin/administration & dosage , Disease-Free Survival , Female , France/epidemiology , Humans , Idarubicin/administration & dosage , Infant , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/mortality , Leukemia, Myelomonocytic, Acute/genetics , Life Tables , Male , Middle Aged , Mitoxantrone/administration & dosage , Multicenter Studies as Topic , Prognosis , Randomized Controlled Trials as Topic , Remission Induction , Retrospective Studies , Risk Factors , Survival Analysis , Treatment Outcome
16.
Blood ; 99(10): 3517-23, 2002 May 15.
Article in English | MEDLINE | ID: mdl-11986202

ABSTRACT

While the t(8;21) translocation is one of the most recurrent chromosomal abnormalities in acute myeloid leukemia, prognostic studies have been hampered by the relatively few number of patients reported. We thus performed a large retrospective study in 161 adults and children with t(8;21) acute myeloid leukemia, all prospectively enrolled in 6 different trials conducted in France between 1987 and 1998 (median follow-up 4.9 years). Prognostic studies were performed in the 154 patients who achieved a complete remission. Individual data were registered, including sex, age, blood and marrow counts, extramedullary disease, and cytogenetics. The value of allogeneic stem cell transplantation versus chemotherapy as postremission therapy was evaluated according to the intent-to-treat principle. Estimated 5-year disease-free survival (DFS) and overall survival were 52% and 59%, respectively. Outcome was not significantly better in patients from the stem cell transplantation group (estimated 5-year DFS and survival, 56% vs 52% and 67% vs 57%; P =.55 and.64, respectively). White blood cell count (WBC) was the only identified prognostic factor. To further take into account the spontaneous differentiation potential of the leukemic clone, a WBC index was derived as the product of WBC by the ratio of marrow blast. This WBC index was a more powerful factor than the original WBC, allowing us to distinguish 3 subgroups of patients with different outcomes (low index, < 2.5; intermediate index, 2.5-20; high index, 20 or more). In multivariate analysis, the WBC index was the only prognostic factor for DFS (P =.003), complete remission duration (P =.002), and overall survival (P =.04).


Subject(s)
Leukemia, Myeloid/diagnosis , Leukocyte Count/methods , Translocation, Genetic , Acute Disease , Adolescent , Adult , Cell Differentiation , Child , Child, Preschool , Chromosomes, Human, Pair 21 , Chromosomes, Human, Pair 8 , Cytogenetic Analysis , Demography , Disease-Free Survival , Female , France , Hematopoietic Stem Cell Transplantation , Hematopoietic Stem Cells/cytology , Humans , Leukemia, Myeloid/genetics , Leukemia, Myeloid/mortality , Leukemia, Myeloid/therapy , Male , Middle Aged , Multicenter Studies as Topic , Multivariate Analysis , Prognosis , Remission Induction , Retrospective Studies
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