Retrospective studies have shown that adolescents and young adults with acute lymphoblastic leukemia (ALL) treated with pediatric protocols have better outcomes than similarly aged patients treated ...with adult protocols, but prospective studies comparing adolescents and young adults using pediatric schedules are scarce. The ALL-96 protocol was addressed to compare the toxicity and results of a pediatric-based protocol in adolescents (age 15-18 years) and young adults (age 19-30 years) with standard-risk (SR) ALL.
Adolescents (n = 35) and young adults (n = 46) received a standard five-drug/5-week induction course followed by two cycles of early consolidation, maintenance with monthly reinforcement cycles up to 1 year in continuous complete remission (CR) and 1 year with standard maintenance chemotherapy up to 2 years in CR.
Adolescents and young adults were comparable in the main pretreatment ALL characteristics. The CR rate was 98% and. after a median follow-up of 4.2 years, 6-year event-free survival (EFS) and overall survival (OS) were 61% (95% CI, 51% to 72%) and 69% (95% CI, 59% to 79%), respectively, with no differences between adolescents and young adults. The hematologic toxicity in consolidation and reinforcement cycles was higher in young adults than in adolescents. Slow response to induction therapy was the only parameter associated with poor EFS (34% v 67%) and OS (40% v 76%).
The response to the pediatric ALL-96 protocol was identical in adolescents and young adults despite a slight increase in hematologic toxicity observed in adults. This justifies the age-unrestricted use of pediatric regimens to treat patients with SR ALL.
The outcome of relapsed adult acute lymphoblastic leukemia (ALL) remains dismal despite new therapeutic approaches. Previous studies analyzing relapse samples have shown a high degree of ...heterogeneity regarding gene alterations without an evident relapse signature. Bone marrow or peripheral blood samples from 31 adult B‐cell precursor ALL patients at first relapse, and 21 paired diagnostic samples were analyzed by multiplex ligation probe‐dependent amplification (MLPA). Nineteen paired diagnostic and relapse samples of these 21 patients were also analyzed by SNP arrays. A trend to acquire homozygous CDKN2A/B deletions and a significant increase in the number of copy number alterations (CNA) was observed from diagnosis to first relapse. Evolution from an ancestral clone was the main pattern of clonal evolution. Relapse samples were extremely heterogeneous regarding CNA frequencies. However, CDKN2A/B, PAX5, ETV6, ATM, IKZF1, VPREB1, and TP53 deletions and duplications of 1q, 8q, 17q, 21, X/Y PAR1, and Xp were frequently detected at relapse. Duplications of genes involved in cell proliferation, drug resistance and stem cell homeostasis regulation, as well as deletions of KDM6A and STAG2 genes emerged as specific alterations at relapse. Genomics of relapsed adult B‐cell precursor ALL is highly heterogeneous, although some recurrent lesions involved in essential pathways deregulation were frequently observed. Selective and simultaneous targeting of these deregulated pathways may improve the results of current salvage therapies.
Chromosomal abnormalities are detected in 20-30% of patients with chronic myelomonocytic leukemia (CMML) and correlate with prognosis. On the mutation level, disruptive alterations are particularly ...frequent in chromatin regulatory genes. However, little is known about the consequential alterations in the epigenetic marking of the genome. Here, we report the analysis of genomic DNA methylation patterns of 64 CMML patients and 10 healthy controls, using a DNA methylation microarray focused on promoter regions. Differential methylation analysis between patients and controls allowed us to identify abnormalities in DNA methylation, including hypermethylation of specific genes and large genome regions with aberrant DNA methylation. Unsupervised hierarchical cluster analysis identified two main clusters that associated with the clinical, biological, and genetic features of patients. Group 1 was enriched in patients with adverse clinical and biological characteristics and poorer overall and progression-free survival. In addition, significant differences in DNA methylation were observed between patients with low risk and intermediate/high risk karyotypes and between TET2 mutant and wild type patients. Taken together, our results demonstrate that altered DNA methylation patterns reflect the CMML disease state and allow to identify patient groups with distinct clinical features.
Highlights • We examined the incidence and impact of ESHAP nephrotoxicity in lymphoma patients. • Nephrotoxicity was more common in outpatients than inpatients (14/39 vs. 4/35). • Patients with renal ...failure at the time of ASCT had an inferior overall survival. • Outpatient administration of ESHAP may not be optimal for all patients.
Abstract Background aims Failure in mobilization of peripheral blood (PB) stem cells is a frequent reason for not performing hematopoietic stem cell transplantation (HSCT). Early identification of ...poor mobilizers could avoid repeated attempts at mobilization, with the administration of pre-emptive rescue mobilization Methods Data from the first mobilization schedule of 397 patients referred consecutively for autologous HSCT between 2000 and 2010 were collected. Poor mobilization was defined as the collection of < 2 × 106 CD34+ cells/kg body weight (BW). Results The median age was 53 years (range 4–70) and 228 (57%) were males. Diagnoses were multiple myeloma in 133 cases, non-Hodgkin's lymphoma in 114, acute myeloid leukemia or myelodysplastic syndrome in 81, Hodgkin's lymphoma in 42, solid tumors in 17 and acute lymphoblastic leukemia in 10. The mobilization regimen consisted of recombinant human granulocyte–colony-stimulating factor (G-CSF) in 346 patients (87%) and chemotherapy followed by G-CSF (C + G-CSF) in 51 (13%). Poor mobilization occurred in 105 patients (29%), without differences according to mobilization schedule. Diagnosis, previous therapy with purine analogs and three or more previous chemotherapy lines were predictive factors for poor mobilization. A CD34+ cell count in PB > 13.8/μL was enough to ensure ≥ 2 × 106 CD34+ cells/kg, with high sensitivity (90%) and specificity (91%). Conclusions The prevalence of poor mobilization was high, being associated with disease type, therapy with purine analogs and multiple chemotherapy regimens. The threshold of CD34+ cell count in PB identified poor mobilizers, in whom the administration of immediate or pre-emptive plerixafor could be useful to avoid a second mobilization.
Patients who are admitted to the intensive care unit (ICU) with hematologic malignancies have a poor prognosis, although outcomes have improved in recent years. This study analyzed ICU mortality, ...short- and long-term survival, and prognostic factors for 100 consecutive critically ill patients with a hematologic malignancy who were admitted to our polyvalent ICU from January 2000 to May 2006. The median age was 55 years (range, 15-75 years; male-female ratio, 60:40). The main acute life-threatening diseases precipitating ICU transfer were respiratory failure (45 patients, 45%) and septic shock (33 patients, 33%). Forty-two patients (42%) were discharged from the ICU. The ICU mortality rate from 2004 to 2006 was lower than from 2000 to 2003 (49% versus 69%, P < .047). The 1- and 2-year probabilities of survival for patients discharged from the ICU were 67% (95% confidence interval CI, 51%-84%) and 54% (95% CI, 34%-73%), respectively. A multivariate analysis revealed hemodynamic instability (odds ratio, 2.11; 95% CI, 1.17-3.83; P = .014) and mechanical ventilation (odds ratio, 4.27; 95% CI, 1.70-10.74; P = .002) to be the main predictors of a poor survival prognosis. Almost half of patients with hematologic malignancy and life-threatening complications can be discharged from the ICU. Age and underlying disease characteristics do not influence ICU outcome, which is mainly determined by hemodynamic and ventilatory status.
1 Department of Hematology, Institut Català dOncologia and
2 Department of Pathology, Hospital Germans Trias i Pujol, Badalona, Universitat Autònoma de Barcelona, Spain
Correspondence: José-Tomás ...Navarro, Department of Hematology, Institut Català dOncologia, Hospital Germans Trias i Pujol, Badalona, Ctra. De Canyet s/n, 08916, Badalona, Barcelona, Spain. Phone: international +34.9.34978868. E-mail: jtnavarr{at}ico.scs.es
We evaluated the frequency of primary central nervous system lymphoma and leptomeningeal involvement in systemic non-Hodgkins lymphoma (NHL) in HIV-infected patients. Those receiving highly active antiretroviral therapy (HAART) showed a decrease in leptomeningeal involvement in systemic NHL (0/30 vs. 12/87; p =0.023). Therefore HAART could prevent CNS involvement in systemic NHL.
Key words: frequency, meningeal, AIDS, lymphoma.
Minimal residual disease (MRD) is an important prognostic factor in adults with acute lymphoblastic leukemia (ALL) and may be used for treatment decisions. The Programa Español de Tratamientos en ...Hematología (PETHEMA) ALL-AR-03 trial (Treatment of High Risk Adult Acute Lymphoblastic Leukemia LAL-AR/2003) assigned adolescent and adult patients (age 15 to 60 years) with high-risk ALL (HR-ALL) without the Philadelphia (Ph) chromosome to chemotherapy or to allogeneic hematopoietic stem-cell transplantation (allo-HSCT) according to early cytologic response (day 14) and flow-MRD level after consolidation.
Patients with good early cytologic response (< 10% blasts in bone marrow at day 14 of induction) and a flow-MRD level less than 5 × 10(-4) at the end of consolidation were assigned to delayed consolidation and maintenance therapy, and allo-HSCT was scheduled in patients with poor early cytologic response or flow-MRD level ≥ 5 × 10(-4).
Complete remission was attained in 282 (87%) of 326 patients, and 179 (76%) of 236 patients who completed early consolidation were assigned by intention-to treat to receive allo-HSCT (71) or chemotherapy (108). Five-year disease-free survival (DFS) and overall survival (OS) probabilities were 37% and 35% for the whole series, 32% and 37% for patients assigned to allo-HSCT, and 55% and 59% for those assigned to chemotherapy. Multivariable analysis showed poor MRD clearance (≥ 1 × 10(-3) after induction and ≥ 5 × 10(-4) after early consolidation) as the only prognostic factor for DFS and OS.
Prognosis for Ph-negative HR-ALL in adolescents and adults with good early response to induction and low flow-MRD levels after consolidation is quite favorable when allo-HSCT is avoided. In this study, the pattern of MRD clearance was the only prognostic factor for DFS and OS.
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