ABSTRACT
PURPOSE: Patients with primary immunodeficiency (PID) are at risk of serious complications. However, data on the incidence and causes of emergency hospital admissions are scarce. The primary objective of the present study was to describe emergency hospital admissions among patients with PID, with a view to identifying "at-risk" patient profiles. METHODS: We performed a prospective observational 12-month multicenter study in France via the CEREDIH network of regional PID reference centers from November 2010 to October 2011. All patients with PIDs requiring emergency hospital admission were included. RESULTS: A total of 200 admissions concerned 137 patients (73 adults and 64 children, 53% of whom had antibody deficiencies). Thirty admissions were reported for 16 hematopoietic stem cell transplantation recipients. When considering the 170 admissions of non-transplant patients, 149 (85%) were related to acute infections (respiratory tract infections and gastrointestinal tract infections in 72 (36%) and 34 (17%) of cases, respectively). Seventy-seven percent of the admissions occurred during winter or spring (December to May). The in-hospital mortality rate was 8.8% (12 patients); death was related to a severe infection in 11 cases (8%) and Epstein-Barr virus-induced lymphoma in 1 case. Patients with a central venous catheter (n = 19, 13.9%) were significantly more hospitalized for an infection (94.7%) than for a non-infectious reason (5.3%) (p = 0.04). CONCLUSION: Our data showed that the annual incidence of emergency hospital admission among patients with PID is 3.4%. The leading cause of emergency hospital admission was an acute infection, and having a central venous catheter was associated with a significantly greater risk of admission for an infectious episode.
Subject(s)
Emergency Medical Services , Hospitalization , Primary Immunodeficiency Diseases/epidemiology , Adult , Child , Communicable Disease Control , Communicable Diseases/etiology , Disease Management , France/epidemiology , Humans , Incidence , Pre-Exposure Prophylaxis , Primary Immunodeficiency Diseases/diagnosis , Primary Immunodeficiency Diseases/etiology , Primary Immunodeficiency Diseases/therapy , Public Health Surveillance , Treatment OutcomeABSTRACT
The aim of our study was to analyze the factors contributing to heterogeneity of prognosis in patients with hyperdiploidy>50 chromosomes (HD>50), a group of B-cell precursor acute lymphoblastic leukemia with favorable outcome. The 541 HD>50 patients registered prospectively in the 58951 European Organisation for Research and Treatment of Cancer (EORTC) Children's Leukemia Group (CLG) trial, identified by karyotype (446 patients) and by DNA index (DI) (490 patients), had a 6-year event-free survival (EFS) of 89.0% (standard error [SE] = 1.5%) and a 6-year overall survival (OS) of 95.9% (SE = 0.9%). The strongest prognostic factor was the modal number of chromosomes (MNC): the 6-year EFS of 51-53, 54-57, and 58-66 MNC groups were 80%, 89%, and 99%, respectively (P < .0001). Ploidy assessed by DI was also a favorable factor: the higher the DI, the better the outcome. The 6-year EFS of the 3 subgroups of DI < 1.16/≥1.16-<1.24/≥1.24 were 83%, 90%, and 95%, respectively (P = .009). All usual combinations of trisomies (chromosomes 4, 10, 17, 18) were significant favorable factors but had lower EFS when MNC was lower than 58. In multivariate analysis, MNC remained the strongest factor. Consequently, the best indicator for excellent outcome was ploidy assessed by karyotype because patients with 58-66 chromosomes stood every chance of being cured (OS of 100% at 6-year follow-up) with less-intensive therapy. This trial was registered at www.clinicaltrials.gov as #NCT00003728. Registered: http://www.eortc.org/, http://clinicaltrials.gov/show/NCT00003728.
Subject(s)
Clinical Trials as Topic , Diploidy , Polyploidy , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/therapy , Adolescent , Age of Onset , Child , Child, Preschool , Chromosome Aberrations/statistics & numerical data , Chromosomes/genetics , Clinical Trials as Topic/methods , Female , Follow-Up Studies , Genetic Heterogeneity , Humans , Infant , Infant, Newborn , Karyotyping , Male , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/epidemiology , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/pathology , Remission InductionABSTRACT
BACKGROUND: Clofarabine alone or in combination with cyclophosphamide and etoposide has shown a good efficacy and a tolerable toxicity profile in previous studies of children with relapsed or refractory leukaemia. This report describes a retrospective study of 38 French patients who received clofarabine as a monotherapy or in combination for relapsed or refractory acute lymphoblastic leukaemia (ALL) outside of clinical trials after marketing authorization. METHODS: We retrospectively analysed data for 38 patients, up to 21 years old, attending 17 French centres. Thirty patients received clofarabine alone or in combination for a bone marrow relapse of acute lymphoblastic leukaemia (ALL) or refractory disease and eight patients for a high level of minimal residual disease (MRD). Survival and response durations were estimated by the Kaplan-Meier method. RESULTS: For the 30 patients who received clofarabine for a bone marrow relapse of ALL (number of relapse, 1-3; median, 1), the overall remission rate (ORR) was 37%: eight complete remission (CR) and three complete remission without platelet recovery (CRp). Ten of the 11 responding patients subsequently underwent haematopoietic stem cell transplantation (HSCT).Only four of the eight patients who received clofarabine while in remission for a high level of MRD, showed a moderate improvement of MRD. Seven of these eight patients received HSCT and six of them were alive at the end of the study. One other patient was alive without receiving HSCT.However, clofarabine treatment was associated with a high risk of infection and hepatotoxicity. Febrile neutropenia grade ≥ 3 was reported in 79% of patients and documented infections grade ≥ 3 occurred in nine patients (24%). Hepatotoxicity grade 3 was reported in nine patients (24%). We observed four deaths related to treatment. CONCLUSION: In our experience, the efficacy of clofarabine is poorer than previously reported. Its toxicity is high and can be life threatening. Prospective studies on clofarabine used during earlier phases of the disease may help to define how best this new drug can be exploited for childhood and adolescent ALL.
ABSTRACT
BACKGROUND: Patients with the Shwachman-Diamond syndrome often develop hematologic complications. No risk factors for these complications have so far been identified. The aim of this study was to classify the hematologic complications occurring in patients with Shwachman-Diamond syndrome and to investigate the risk factors for these complications. DESIGN AND METHODS: One hundred and two patients with Shwachman-Diamond syndrome, with a median follow-up of 11.6 years, were studied. Major hematologic complications were considered in the case of definitive severe cytopenia (i.e. anemia <7 g/dL or thrombocytopenia <20 × 10(9)/L), classified as malignant (myelodysplasia/leukemia) according to the 2008 World Health Organization classification or as non-malignant. RESULTS: Severe cytopenia was observed in 21 patients and classified as malignant severe cytopenia (n=9), non-malignant severe cytopenia (n=9) and malignant severe cytopenia preceded by non-malignant severe cytopenia (n=3). The 20-year cumulative risk of severe cytopenia was 24.3% (95% confidence interval: 15.3%-38.5%). Young age at first symptoms (<3 months) and low hematologic parameters both at diagnosis of the disease and during the follow-up were associated with severe hematologic complications (P<0.001). Fifteen novel SBDS mutations were identified. Genotype analysis showed no discernible prognostic value. CONCLUSIONS Patients with Shwachman-Diamond syndrome with very early symptoms or cytopenia at diagnosis (even mild anemia or thrombocytopenia) should be considered at a high risk of severe hematologic complications, malignant or non-malignant. Transient severe cytopenia or an indolent cytogenetic clone had no deleterious value.
Subject(s)
Bone Marrow Diseases/complications , Exocrine Pancreatic Insufficiency/complications , Hematologic Diseases/classification , Hematologic Diseases/etiology , Lipomatosis/complications , Bone Marrow Diseases/mortality , Exocrine Pancreatic Insufficiency/mortality , Female , Follow-Up Studies , France , Hematologic Diseases/mortality , Humans , Infant , Lipomatosis/mortality , Male , Prognosis , Prospective Studies , Registries , Risk Factors , Shwachman-Diamond Syndrome , Survival RateABSTRACT
AIM OF THE STUDY: To determine whether a risk factor adapted chemotherapy would improve the outcome of non-metastatic bone Ewing's sarcoma. METHODS: Standard risk tumours (SR, good histological response to chemotherapy or small unresected tumours) received the previous EW88 chemotherapy. Ifosfamide/etoposide (IE) were introduced after 3 courses of cyclophosphamide/doxorubicine when tumour regression was <50% or during consolidation therapy for the intermediate risk tumours (IR, intermediate histological response 5-30% residual cells or large unresected tumours >100ml). High risk tumours (HR, histological poor response >30% residual cells or clinical poor response <50% for unresectable tumours), received IE prior high dose busulfan/melphalan with stem cell rescue. RESULTS: From 1993 to 1999, 214 patients were enrolled. 5 y-EFS and OS were 60% (95% confidence interval (CI), 53-66) and 69% (95% CI, 63-75), respectively. 116 (54%), 46 (21%), 48 (22%) patients were considered as SR, IR and HR of relapse, respectively. No advantage to IE was observed in the IR group. As compared to previous study, tumour with poor histological response to induction chemotherapy seemed to benefit from the consolidation strategy including busulfan/melphalan: EFS were 45% (95% CI, 30-60) and 20% (95% CI, 7-43) for EW93 and EW88, respectively. Despite a risk-adapted strategy, histological response to chemotherapy remains the main prognostic factor in resected tumours, while initial tumour volume is the main prognostic factor for unresected tumours. CONCLUSION: These results showing a potential benefit of a consolidation strategy including busulfan/melphalan as compared to conventional chemotherapy needed confirmation by a randomised trial and were one of the bases of the ongoing EuroEwing99.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bone Neoplasms/drug therapy , Sarcoma, Ewing/drug therapy , Adolescent , Adult , Child , Child, Preschool , Drug Administration Schedule , Female , Follow-Up Studies , France , Humans , Infant , Male , Prognosis , Risk Factors , Treatment Outcome , White People , Young AdultABSTRACT
BACKGROUND: Intensive chemotherapy has markedly improved the survival of children with acute lymphoblastic leukaemia (ALL) or lymphoblastic lymphoma (LL). Evaluation of late effects and analysis of factors contributing to their occurrence has become of major importance. Second neoplasm (SN) belongs to the most severe late events. PROCEDURE: We report the incidence of SN which occurred in patients recruited in EORTC trial 58881 for children with ALL or LL. The front-line treatment regimen was adapted from the BFM protocol, but did not include cranial radiotherapy, even in patients with initial involvement of the central nervous system. A total of 2,216 patients were recruited, of whom 2,136 achieved complete remission (CR). RESULTS: At a median follow-up of 7.5 years, 22 (1%) patients developed a SN: 20 during or after completion of front-line therapy and 2 in second CR, after relapse treatment including haematopoietic stem cell transplantation (HSCT). Ten patients developed acute myeloblastic leukaemia. Only one SN, a glioblastoma, was a brain tumour. Other SN were: two Hodgkin lymphomas, one non-Hodgkin lymphoma, two thyroid cancers, one osteosarcoma, two soft tissue sarcomas, one Ewing sarcoma, one cutaneous histiocytosis and one peritoneal carcinomatosis. The cumulative incidences of SN at 5, 8 and 13 years after registration were 0.8% (SE 0.2%), 1.0% (SE 0.2%) and 3.0% (SE 1.9%), respectively. CONCLUSION: The overall incidence rate of SN is comparable to that reported previously. In spite of short follow-up time, the low incidence of brain tumours might be related to the omission of cranial radiotherapy.
Subject(s)
Central Nervous System Neoplasms/mortality , Neoplasms, Second Primary/mortality , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Adolescent , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Asparaginase/administration & dosage , Asparaginase/adverse effects , Central Nervous System Neoplasms/therapy , Child , Child, Preschool , Clinical Trials as Topic , Daunorubicin/administration & dosage , Daunorubicin/adverse effects , Disease-Free Survival , Female , Follow-Up Studies , Humans , Incidence , Infant , Male , Neoplasms, Second Primary/therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Prednisone/administration & dosage , Prednisone/adverse effects , Remission Induction , Retrospective Studies , Survival Rate , Vincristine/administration & dosage , Vincristine/adverse effectsABSTRACT
The European Organisation for Research and Treatment of Cancer 58951 trial for children with acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL) addressed 3 randomized questions, including the evaluation of dexamethasone (DEX) versus prednisolone (PRED) in induction and, for average-risk patients, the evaluation of vincristine and corticosteroid pulses during continuation therapy. The corticosteroid used in the pulses was that assigned at induction. Overall, 411 patients were randomly assigned: 202 initially randomly assigned to PRED (60 mg/m(2)/d), 201 to DEX (6 mg/m(2)/d), and 8 nonrandomly assigned to PRED. At a median follow-up of 6.3 years, there were 19 versus 34 events for pulses versus no pulses; 6-year disease-free survival (DFS) rate was 90.6% (standard error [SE], 2.1%) and 82.8% (SE, 2.8%), respectively (hazard ratio [HR] = 0.54; 95% confidence interval, 0.31-0.94; P = .027). The effect of pulses was similar in the PRED (HR = 0.56) and DEX groups (HR = 0.59) but more pronounced in girls (HR = 0.24) than in boys (HR = 0.71). Grade 3 to 4 hepatic toxicity was 30% versus 40% in pulses versus no pulses group and grade 2 to 3 osteonecrosis was 4.4% versus 2%. For average-risk patients treated according to Berlin-Frankfurt-Muenster-based protocols, pulses should become a standard component of therapy.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, Non-Hodgkin/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Adrenal Cortex Hormones/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Chemical and Drug Induced Liver Injury/etiology , Child , Child, Preschool , Dexamethasone/administration & dosage , Female , Humans , Infant , Lymphoma, Non-Hodgkin/diagnosis , Lymphoma, Non-Hodgkin/mortality , Male , Osteonecrosis/chemically induced , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Prednisolone/administration & dosage , Survival Analysis , Survival Rate , Treatment Outcome , Vincristine/administration & dosageABSTRACT
BACKGROUND: Bilateral adrenal neuroblastoma is extremely rare. To date, 45 cases have been reported in the literature. PROCEDURES: We retrospectively identified and reviewed 15 cases of bilateral adrenal neuroblastoma, treated between 1988 and 2004, by the French Society of Pediatric Oncology. We then compared our cohort to the 45 cases reported in literature. RESULTS: Median age at diagnosis was 4 months in our cohort whereas it was 3 months in the literature. The same percentage of infants was found in both series (86.6%). Disease had generally been detected due to metastasis-related symptoms. Ten out of 15 patients in our cohort and 18/39 cases in the literature were classified as stage 4S according to the International Neuroblastoma Staging System (INSS). The incidence of stage 4S was significantly higher than that described in other neuroblastoma cohorts (P = 10(-4)). Five-year overall survival was 90% for stage 4S. In our series, bilateral neuroblastoma was neither associated with familial cases nor with any risk factors. CONCLUSIONS: The majority of bilateral neuroblastoma carry a favorable prognosis. Exceptional cases exhibiting risk factors, such as amplified MYCN, are comparable to high-risk unilateral neuroblastoma cases with the same poor prognostic features. The therapeutic strategy could be similar to that used against unilateral neuroblastoma, except for surgery. However, the low incidence of relapse and the risk of adrenal failure if radical surgery is performed, argue against an aggressive surgical approach.
Subject(s)
Adrenal Gland Neoplasms/epidemiology , Neuroblastoma/epidemiology , Adrenal Gland Neoplasms/mortality , Adrenal Gland Neoplasms/therapy , Antineoplastic Agents/therapeutic use , Female , France , Humans , Infant , Infant, Newborn , Male , N-Myc Proto-Oncogene Protein , Neuroblastoma/mortality , Neuroblastoma/therapy , Nuclear Proteins/genetics , Oncogene Proteins/genetics , Pregnancy , Radiotherapy , Retrospective Studies , Risk Factors , Treatment OutcomeABSTRACT
Gemtuzumab ozogamicin (GO) monotherapy is reported to yield a 20-30% response rate in advanced acute myeloid leukaemia (AML). This study examined the efficacy and tolerability of GO combined with cytarabine (GOCYT) in children with refractory/relapsed CD33(+) AML. Seventeen children received GO 3 mg/m(2) on days 1, 4 and 7 plus cytarabine 100 mg/m(2)/d for 7 d on a compassionate-use basis. Seven patients then received GO-based consolidation. At the outset of GOCYT, two patients were refractory; eight patients were in refractory first relapse; six patients had relapsed after stem cell transplantation (SCT); and one patient [del(5q) therapy-related AML (t-AML)] had not yet been treated. Mean follow-up was 17 months (8-33 months). Ten responses were obtained after GOCYT induction, including complete remission (CR) or CR without complete recovery of platelets (CRp) in six patients (35%). The responses improved in three children who received GOCYT consolidation, increasing the CR + CRp rate to 53%. SCT was subsequently performed in eight responders. Grade 3-4 adverse events consisted of haematological disorders (n = 17, 100%) and documented infections (n = 5, 29%). No cases of sinusoidal obstructive syndrome occurred. Three patients were alive at the cut-off date for this analysis, all of whom had responded to GOCYT. GOCYT combination therapy yielded a high response rate (53%) and showed acceptable toxicity in heavily pretreated children with refractory/relapsed AML. These results warrant a larger prospective study.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Leukemia, Myeloid, Acute/drug therapy , Adolescent , Aminoglycosides/administration & dosage , Aminoglycosides/adverse effects , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Child , Child, Preschool , Cytarabine/administration & dosage , Cytarabine/adverse effects , Drug Administration Schedule , Drug Evaluation , Epidemiologic Methods , Female , Gemtuzumab , Humans , Infant , Male , Recurrence , Treatment OutcomeABSTRACT
PURPOSE: Many cooperative groups have reported on the chemo-sensitivity of rhabdomyosarcoma (RMS). Doxorubicin has been tested but remains a controversial treatment option. We report here the results of the up-front evaluation of the efficacy of doxorubicin in children and adolescents with high-risk metastatic RMS. PATIENTS AND METHODS: Patients younger than 18 years of age (>6 months) with newly diagnosed, histologically confirmed high-risk metastatic RMS were required to have measurable disease, to have undergone no prior chemotherapy or radiation therapy and to have normal liver, renal and cardiac function before treatment. Doxorubicin was administered intravenously over 48h to a total dose of 60mg/m2. Two courses were given separated by a 21day interval. Response to therapy was assessed by diagnostic imaging after the second course. The study was designed as a two-stage procedure according to the multistep plan described by Fleming. RESULTS: Twenty patients were eligible for analysis. Median age at diagnosis was 9.8 years (range from 2 to 16). Thirteen of the 20 patients treated in the first step responded to treatment, corresponding to an overall response to doxorubicin of 65% [95% confidence interval (CI), 44-85%]. The rates of CR and PR were 5% [95% CI, 0-14%] and 60% [95% CI, 39-81%], respectively. Four (20%) patients had progressive disease, corresponding to a progression rate of 20% [95% CI, 2-38%]. CONCLUSION: This window study provides the definitive demonstration of the efficacy of doxorubicin in untreated RMS. Given the inconclusive results obtained from previous studies using differing schedules chemotherapy incorporating doxorubicin, the next step should be a randomised study testing dose intensity in high-risk localised RMS. This issue is being addressed in a current European study (EpSSG RMS 2005).
Subject(s)
Antibiotics, Antineoplastic/administration & dosage , Doxorubicin/administration & dosage , Rhabdomyosarcoma/drug therapy , Soft Tissue Neoplasms/drug therapy , Adolescent , Analysis of Variance , Antibiotics, Antineoplastic/adverse effects , Child , Child, Preschool , Doxorubicin/adverse effects , Drug Administration Schedule , Female , Humans , Infusions, Intravenous , Male , Rhabdomyosarcoma/secondary , Treatment OutcomeABSTRACT
A case-control study was conducted to investigate the role of a familial history of cancer in the etiology of childhood acute leukemia. The history of cancer in the relatives of 472 cases was compared with that of 567 population-based controls. Recruitment was frequency matched on age, sex and region. The familial history of cancer in each child's relatives was reported by the mother in response to a standardized self-administered questionnaire. A familial history of solid tumor in first or second-degree relatives was associated with an increased risk of acute lymphoblastic leukemia (odds ratio (OR)=1.6 [95% confidence interval, 1.2-2.1]), while a familial history of hematopoietic malignancies in first or second-degree relatives was associated with an increased risk of acute myeloid leukemia (OR=4.3 [1.4-13]). The ORs for the histories of cancer increased with the number of relatives with cancer (OR=1.5 [1.1-2.0] for one relative and OR=2.3 [1.3-3.8] for two relatives or more; Ptrend<0.0001). Significant associations between childhood acute leukemia and familial history of genital cancers and brain tumor were also observed (OR=2.7 [1.2-5.8] and OR=10.7 [1.3-86], respectively). This study supports the hypothesis that a familial history of cancer may play a role in the etiology of childhood acute leukemia. It also evidences some specific associations that require further investigation.
Subject(s)
Leukemia/genetics , Neoplasms/genetics , Acute Disease , Adolescent , Case-Control Studies , Child , Child, Preschool , Family , Female , Humans , Infant , Infant, Newborn , MaleABSTRACT
The properties of saliva led us to hypothesize that the salivary flow increase induced by gum chewing might protect the oral mucosa from lesions due to cancer chemotherapy. We conducted a multicenter randomized trial to evaluate the efficacy of chewing gum in preventing oral mucositis in 145 children receiving chemotherapy regimens expected to induce WHO grade 3-4 oral mucositis in at least 30% of patients. Patients were allocated at random to standard oral care with or without 5 gum pieces per day. No overall reduction in severe oral mucositis occurred in the gum arm (51%) compared with the standard arm (44%). VIDE, COPADM, and multidrug intensive chemotherapy caused severe oral mucositis in 75% of patients in both arms. In patients receiving less toxic regimens, a decrease in WHO grade 1-4 oral mucositis was noted in the gum arm compared with the standard arm (49% vs. 72%, P=0.03). In the multivariate analysis, the risk of oral mucositis was related only to the type of chemotherapy regimen, suggesting that further strategies for preventing oral mucositis could be mainly based on these criteria.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Chewing Gum , Stomatitis/prevention & control , Adolescent , Child , Child, Preschool , Female , Humans , Male , Neoplasms/drug therapy , Risk Factors , Stomatitis/chemically inducedABSTRACT
BACKGROUND AND OBJECTIVES: Deletion and methylation of the 9p21 chromosomal region are frequent in childhood acute lymphoblastic leukemia (ALL) but the prognostic significance is controversial. They inactivate CDKN2A, a gene encoding both p16INKa and p14ARF and, in some cases, contiguous genes that may influence chemosensitivity, such as CDKN2B encoding p15INKb or MTAP encoding methylthioadenosine phosphorylase. DESIGN AND METHODS: CDKN2A inactivation by deletion or methylation was studied using gene dosage and methyl-specific polymerase chain reaction. RESULTS: Bi-allelic and mono-allelic inactivation were found in, respectively, 38 (17%) and 31 (14%) of 227 children with B-lineage ALL enrolled in EORTC trials. Although CDKN2A inactivation was more often associated with poor prognostic features in B-lineage ALL, it failed to influence the outcome of the patients significantly. Bi-allelic CDKN2B and MTAP co-inactivation were found in 36 (16%) and 24 (11%) of patients, respectively, and did not influence the 6-year event-free survival rate either, even when the analysis was restricted to CDKN2A inactivated ALL. INTERPRETATION AND CONCLUSIONS: In this study of 227 cases of childhood B-lineage ALL, inactivation of CDKN2A, CDKN2B and MTAP did not influences the patients' outcome.
Subject(s)
Gene Silencing , Neoplasm Proteins/genetics , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Adolescent , Child , Child, Preschool , Cyclin-Dependent Kinase Inhibitor p15/genetics , Cyclin-Dependent Kinase Inhibitor p16/genetics , Humans , Infant , Microtubule-Associated Proteins/genetics , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/mortality , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Prognosis , Survival Rate , Treatment OutcomeABSTRACT
In a series of 153 children with T-cell malignancies enrolled in 2 consecutive European Organization for Research and Treatment of Cancer (EORTC) trials, we assessed the HOX11L2 expression and/or the presence of a t(5;14)(q35;q32). Additionally, in 138 of these patients, HOX11 expression and SIL-TAL rearrangement were also assessed. These alterations were mutually exclusive, and their frequency was 23% (n = 35), 7% (n = 10), and 12% (n = 17), respectively. HOX11L2/t(5;14) positivity was more frequent in acute lymphoblastic leukemia (ALL) with cortical T immunophenotype and in children aged between 6 and 9 years. In contrast with previously reported data, patients positive and negative for HOX11L2/t(5;14) were comparable with regard to clinical outcome as well as to the response to a 7-day prephase treatment or to residual disease at completion of induction therapy. The 3-year event-free survival (EFS) rate (+/- SE percentage) for patients positive and negative for HOX11L2/t(5;14) was 75.5% (+/- 8.1%) and 68.3% (+/- 5.0%), respectively; the hazard ratio was 0.84 (95% confidence interval, 0.40-1.80). Patients with HOX11-high expression and those with SIL-TAL fusion had low levels of residual disease at the end of induction and a favorable prognosis: the 3-year EFS rate was 83.3% (+/- 8.5%) and 75.3% (+/- 12.6%), respectively. The results obtained in HOX11L2/t(5;14) patients in this study do not confirm the unfavorable prognosis reported in previous studies.