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1.
Haematologica ; 109(2): 543-552, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-37560813

ABSTRACT

High dose-intensive or infusional intermediate-dose immunochemotherapy is highly effective treatment for Burkitt lymphoma irrespective of human immunodeficiency virus (HIV) infection. However, toxicities of these regimens are relevant, especially in older adults and elderly patients. The prospective multicenter BURKIMAB14 trial included four to six blocks of immunochemotherapy according to stage (localized: 1 and 2 non-bulky; advanced: 2 bulky, 3, 4) and age, with dose reduction in patients >55 years old. Dose-intensity of chemotherapy was reduced in patients ≤55 years old after achieving complete metabolic response (CMR). Their outcomes were compared with those of similar patients included in the former BURKIMAB08 trial, in which there was no dose reduction. CMR was attained in 86 of 107 (80%) patients (17/19 in localized stages and 69/88 in advanced stages). Patients from the BURKIMAB14 trial ≤55 years old showed similar overall survival (OS), fewer infections and cytopenias than patients from the BURKIMAB08 trial. Patients >55 years old had a significantly higher treatment- related mortality despite dose reduction of chemotherapy. With a median follow-up of 3.61 years the 4-year OS probability was 73% (range, 63-81%). Age (≤55 vs. >55 years) and stage (localized vs. advanced) had prognostic significance. No significant differences in OS were observed in HIV-positive versus HIV-negative patients. The results of BURKIMAB14 are similar to those of other dose-intensive immunochemotherapy trials. Age >55 years and advanced stage, but not HIV infection, were associated with poor survival. Dose reduction of chemotherapy in young adults in CMR is safe and does not impact outcomes (clinicaltrials gov. Identifier: NCT05049473).


Subject(s)
Burkitt Lymphoma , HIV Infections , Leukemia , Humans , Young Adult , Aged , Middle Aged , Burkitt Lymphoma/drug therapy , Burkitt Lymphoma/pathology , Drug Tapering , Feasibility Studies , Prospective Studies , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Leukemia/drug therapy , HIV Infections/drug therapy , Cyclophosphamide/therapeutic use , Doxorubicin/therapeutic use , Rituximab/therapeutic use
3.
Haematologica ; 108(4): 969-980, 2023 04 01.
Article in English | MEDLINE | ID: mdl-36325893

ABSTRACT

Genetic information has been crucial to understand the pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL) at diagnosis and at relapse, but still nowadays has a limited value in a clinical context. Few genetic markers are associated with the outcome of T-ALL patients, independently of measurable residual disease (MRD) status after therapy. In addition, the prognostic relevance of genetic features may be modulated by the specific treatment used. We analyzed the genetic profile of 145 T-ALL patients by targeted deep sequencing. Genomic information was integrated with the clinicalbiological and survival data of a subset of 116 adult patients enrolled in two consecutive MRD-oriented trials of the Spanish PETHEMA (Programa Español de Tratamientos en Hematología) group. Genetic analysis revealed a mutational profile defined by DNMT3A/ N/KRAS/ MSH2/ U2AF1 gene mutations that identified refractory/resistant patients. Mutations in the DMNT3A gene were also found in the non-leukemic cell fraction of patients with T-ALL, revealing a possible mutational-driven clonal hematopoiesis event to prime T-ALL in elderly. The prognostic impact of this adverse genetic profile was independent of MRD status on day +35 of induction therapy. The combined worse-outcome genetic signature and MRD on day +35 allowed risk stratification of T-ALL into standard or high-risk groups with significantly different 5- year overall survival (OS) of 52% (95% confidence interval: 37-67) and 17% (95% confidence interval: 1-33), respectively. These results confirm the relevance of the tumor genetic profile in predicting patient outcome in adult T-ALL and highlight the need for novel gene-targeted chemotherapeutic schedules to improve the OS of poor-prognosis T-ALL patients.


Subject(s)
Precursor Cell Lymphoblastic Leukemia-Lymphoma , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma , Humans , Adult , Aged , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Disease-Free Survival , Prognosis , Neoplasm, Residual/genetics , Genomics , T-Lymphocytes/pathology
5.
Hematol Oncol ; 39(4): 529-538, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34405901

ABSTRACT

Despite high complete remission (CR) rates with frontline therapy, relapses are frequent in adults with T-cell acute lymphoblastic leukemia (T-ALL) with limited salvage options. We analyzed the outcomes and prognostic factors for CR to salvage therapy and overall survival (OS) of patients with R/R T-ALL included in two prospective measurable residual disease-oriented trials. Seventy-five patients (70 relapsed, 5 refractory) were identified. Relapses occurred in bone marrow, isolated or combined in 50 patients, and in the central nervous system (CNS; isolated or combined) in 20. Second CR was attained in 30/75 patients (40%). Treatment with FLAG-Ida and isolated CNS relapse were independently associated with a higher CR rate after first salvage therapy. The median OS was 6.2 (95% confidence interval [CI], 3.9-8.6) months, with a 4-year OS probability of 18% (95% CI, 9%-27%). No differences in survival were observed according to the treatment with hematopoietic stem cell transplantation in patients in CR after first salvage therapy. Multivariable analysis showed a ≥12-month interval between first CR and relapse, CR after first salvage therapy and isolated CNS relapse as favorable prognostic factors for OS with hazard ratios (HR) (95% CI) of 1.931 (1.109-3.362), 2.958 (1.640-5.334), and 2.976 (1.157-7.655), respectively. This study confirms the poor outcomes of adults with R/R T-ALL among whom FLAG-Ida was the best of the rescue therapies evaluated. Late relapse, CR after first rescue therapy and isolated CNS relapse showed prognostic impact on survival. More effective rescue therapies are needed in adults with R/R T-ALL.


Subject(s)
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/therapy , Adolescent , Adult , Female , Humans , Male , Middle Aged , Neoplasm, Residual , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/mortality , Prognosis , Treatment Outcome , Young Adult
6.
Leuk Res ; 109: 106612, 2021 10.
Article in English | MEDLINE | ID: mdl-34139642

ABSTRACT

The potential prognostic value of conventional karyotyping in adult T-cell acute lymphoblastic leukemia (T-ALL) remains an open question. We hypothesized that a modified cytogenetic classification, based on the number and type of cytogenetic abnormalities, would allow the identification of high-risk adult T-ALL patients. Complex karyotype defined by the presence of ≥3 cytogenetic alterations identified T-ALL patients with poor prognosis in this study. Karyotypes with ≥3 abnormalities accounted for 16 % (22/139) of all evaluable karyotypes, corresponding to the largest poor prognosis cytogenetic subgroup of T-ALL identified so far. Patients carrying karyotypes with ≥3 cytogenetic alterations showed a significantly inferior response to therapy, and a poor outcome in terms of event-free survival (EFS), overall survival (OS) and cumulative incidence of relapse (CIR), independently of other baseline characteristics and the end-induction minimal residual disease (MRD) level. Additional molecular analyses of patients carrying ≥3 cytogenetic alterations showed a unique molecular profile that could contribute to understand the underlying molecular mechanisms of resistance and to evaluate novel targeted therapies (e.g. IL7R directed) with potential impact on outcome of adult T-ALL patients.


Subject(s)
Chromosome Aberrations , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Adolescent , Adult , Female , Humans , Karyotype , Male , Middle Aged , Neoplasm, Residual/diagnosis , Neoplasm, Residual/genetics , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Prognosis , Young Adult
7.
Blood ; 137(14): 1879-1894, 2021 04 08.
Article in English | MEDLINE | ID: mdl-33150388

ABSTRACT

The need for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adults with Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) with high-risk (HR) features and adequate measurable residual disease (MRD) clearance remains unclear. The aim of the ALL-HR-11 trial was to evaluate the outcomes of HR Ph- adult ALL patients following chemotherapy or allo-HSCT administered based on end-induction and consolidation MRD levels. Patients aged 15 to 60 years with HR-ALL in complete response (CR) and MRD levels (centrally assessed by 8-color flow cytometry) <0.1% after induction and <0.01% after early consolidation were assigned to receive delayed consolidation and maintenance therapy up to 2 years in CR. The remaining patients were allocated to allo-HSCT. CR was attained in 315/348 patients (91%), with MRD <0.1% after induction in 220/289 patients (76%). By intention-to-treat, 218 patients were assigned to chemotherapy and 106 to allo-HSCT. The 5-year (±95% confidence interval) cumulative incidence of relapse (CIR), overall survival (OS), and event-free survival probabilities for the whole series were 43% ± 7%, 49% ± 7%, and 40% ± 6%, respectively, with CIR and OS rates of 45% ± 8% and 59% ± 9% for patients assigned to chemotherapy and of 40% ± 12% and 38% ± 11% for those assigned to allo-HSCT, respectively. Our results show that avoiding allo-HSCT does not hamper the outcomes of HR Ph- adult ALL patients up to 60 years with adequate MRD response after induction and consolidation. Better postremission alternative therapies are especially needed for patients with poor MRD clearance. This trial was registered at www.clinicaltrials.gov as # NCT01540812.


Subject(s)
Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Adolescent , Adult , Consolidation Chemotherapy , Female , Hematopoietic Stem Cell Transplantation , Humans , Induction Chemotherapy , Maintenance Chemotherapy , Male , Middle Aged , Neoplasm, Residual/diagnosis , Neoplasm, Residual/genetics , Philadelphia Chromosome , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Prognosis , Transplantation, Homologous , Treatment Outcome , Young Adult
8.
Clin Lymphoma Myeloma Leuk ; 20(8): e513-e522, 2020 08.
Article in English | MEDLINE | ID: mdl-32336676

ABSTRACT

BACKGROUND: The treatment of acute lymphoblastic leukemia (ALL) in older adults and elderly patients is a challenge, and modern protocols include targeted therapy and immunotherapy in combination with attenuated or minimal chemotherapy. However, frail patients are excluded from these trials, and reports on the outcome of this subgroup of patients are scarce. Our objective was to analyze the outcome of unfit older adults and elderly patients with Philadelphia chromosome-negative ALL included in a prospective trial (ALL-07FRAIL). PATIENTS AND METHODS: Older adults and elderly patients with Charlson Comorbidity Index (CCI) ≥ 4 were included. Induction therapy consisted of vincristine and dexamethasone, and maintenance therapy with mercaptopurine and methotrexate for 2 years. RESULTS: Seventy-two patients with a median age of 67 years (range, 57-89 years) and a median CCI of 5 (range, 4-12) were included. The rates of early withdrawal, early death, resistance, and complete response (CR) were 5%, 10%, 31%, and 54%, respectively. Six patients with CR abandoned the study, 5 died in CR, and 23 relapsed (cumulative relapse incidence 75%). The medians of disease-free and overall survival (OS) were 6.9 months (95% confidence interval [CI], 0.3-13.5 months) and 7.6 months (95% CI, 6.3-8.9 months), respectively. The most frequent toxic events were hematologic (neutropenia 77% and thrombocytopenia 54%, of grade III-IV in all cases). Eastern Cooperative Oncology Group score but not the CCI had significant impact on OS. CONCLUSION: Complete remission with very attenuated chemotherapy can be attained in one-half of older or elderly infirm patients with ALL. These results suggest that some of these patients could benefit from the concomitant or subsequent use of immunotherapy and/or targeted therapy.


Subject(s)
Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Aged , Aged, 80 and over , Female , Frail Elderly , Humans , Male , Middle Aged , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Prospective Studies
10.
Eur J Haematol ; 102(1): 79-86, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30267597

ABSTRACT

OBJECTIVE AND METHODS: Pediatric-inspired regimens have been adopted by several groups as the treatment strategy for adult patients with acute lymphoblastic leukemia (ALL). Whether subsequent modifications of these protocols have led to an improvement in the outcome of patients is uncertain, especially in T-cell ALL. We analyzed 169 patients with high-risk T-cell ALL included in two consecutive trials of the PETHEMA Group (HR-ALL03 [n = 104] and the more contemporary HR-ALL11 [n = 65]). RESULTS: Patients and disease characteristics were balanced between both groups. Regarding efficacy, we observed a similar complete remission (CR) rate, relapse and disease-free survival (DFS) between both protocols. Patients included in the HR-ALL11 trial had better 2-year overall survival (OS) compared with the HR-ALL03 (65% [95% CI 51%-79%] vs 44% [95% CI 34%-54%], P = 0.026). Regarding toxicity, we observed a better safety profile in the HR-11 protocol. Irrespective of the protocol, patients with good measurable residual disease (MRD) clearance had a promising outcome without allogeneic hematopoietic stem cell transplantation (allo-HSCT) in CR1, with 2-year OS of 67%. CONCLUSION: Patients with T-cell ALL included in the HR-11 trial showed better OS than patients in the HR-03, mostly driven by a reduction of NRM.


Subject(s)
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/mortality , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/therapy , Adolescent , Adult , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Combined Modality Therapy , Consolidation Chemotherapy , Female , Genetic Testing , Hematopoietic Stem Cell Transplantation , Humans , Immunophenotyping , Induction Chemotherapy , Male , Middle Aged , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/etiology , Recurrence , Risk Factors , Transplantation, Homologous , Treatment Outcome , Young Adult
11.
BMC Pregnancy Childbirth ; 18(1): 94, 2018 04 11.
Article in English | MEDLINE | ID: mdl-29642862

ABSTRACT

BACKGROUND: Epidural analgesia during labor can provide effective pain relief, but can also lead to adverse effects. The practice of moderate exercise during pregnancy is associated with an increased level of endorphins in the blood, and this could also provide pain relief during labor. Aerobic water exercises, rather than other forms of exercise, do not negatively impact articulations, reduce edema, blood pressure, and back pain, and increase diuresis. We propose a randomized controlled trial (RCT) to evaluate the effectiveness and safety of a moderate water exercise program during pregnancy on the need for epidural analgesia during labor. METHODS: A multi-center, parallel, randomized, evaluator blinded, controlled trial in a primary care setting. We will randomised 320 pregnant women (14 to 20 weeks gestation) who have low risk of complications to a moderate water exercise program or usual care. DISCUSSION: The findings of this research will contribute toward understanding of the effects of a physical exercise program on pain and the need for analgesia during labor. TRIAL REGISTRATION: ISRCTN Registry identifier: 14097513 register on 04 September 2017. Retrospectively registered.


Subject(s)
Analgesia, Epidural/statistics & numerical data , Analgesia, Obstetrical/statistics & numerical data , Exercise Therapy/methods , Prenatal Care/methods , Primary Health Care/methods , Randomized Controlled Trials as Topic , Exercise , Female , Humans , Labor Pain/drug therapy , Pregnancy , Single-Blind Method , Swimming , Treatment Outcome
12.
Leuk Lymphoma ; 59(7): 1634-1643, 2018 07.
Article in English | MEDLINE | ID: mdl-29165013

ABSTRACT

Native or pegylated (PEG) asparaginase (ASP) are commonly used in treatment of acute lymphoblastic leukemia (ALL), but have been scarcely compared in the same trial in adult patients. Native vs. PEG-ASP administered according to availability in each center were prospectively evaluated in adults with high-risk ALL. Ninety-one patients received native ASP and 35 PEG-ASP in induction. No significant differences were observed in complete remission, minimal residual disease levels after induction and after consolidation, disease-free survival, and overall survival. No significant differences in grades 3-4 toxicity were observed in the induction period, although a trend for higher hepatic toxicity was observed in patients receiving PEG-ASP. In this trial the type of ASP did not influence patient response and outcome.


Subject(s)
Asparaginase/therapeutic use , Polyethylene Glycols/therapeutic use , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Adolescent , Adult , Age Factors , Asparaginase/administration & dosage , Asparaginase/adverse effects , Combined Modality Therapy , Female , Humans , Male , Middle Aged , Neoplasm Grading , Neoplasm Staging , Philadelphia Chromosome , Polyethylene Glycols/administration & dosage , Polyethylene Glycols/adverse effects , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Survival Analysis , Treatment Outcome , Young Adult
13.
PLoS One ; 12(6): e0179595, 2017.
Article in English | MEDLINE | ID: mdl-28665999

ABSTRACT

Central nervous system (CNS) lymphomatosis is a fatal complication of aggressive non-Hodgkin lymphoma (NHL). In lymphoblastic or Burkitt lymphoma, without specific CNS prophylaxis the risk of CNS relapse is 20-30%. DLBCL has a lower risk of relapse (around 5%) but several factors increase its incidence. There is no consensus or trials to conclude which is the best CNS prophylaxis. Best results seem to be associated with the use of intravenous (iv) high-dose methotrexate (HDMTX) but with a significant toxicity. Other options are the administration of intrathecal (IT) MTX, cytarabine or liposomal cytarabine (ITLC). Our aim is to analyze the experience of the centers of the Balearic Lymphoma Group (BLG) about the toxicity and efficacy of ITLC in the prophylaxis and therapy of CNS lymphomatosis. We retrospectively reviewed cases from 2005 to 2015 (n = 58) treated with ITLC. Our toxicity results were: 33% headache, 20% neurological deficits, 11% nausea, 9% dizziness, 4% vomiting, 4% fever, 2% transient blindness and 2% photophobia. In the prophylactic cohort (n = 26) with a median follow-up of 55 months (17-81) only 3 CNS relapses (11%) were observed (testicular DLBCL, Burkitt and plasmablastic lymphoma, with a cumulative incidence of 8%, 14% and 20% respectively). In the treatment cohort (n = 32), CSF complete clearance was obtained in 77% cases. Median OS was 6 months (0-16). Death causes were lymphoma progression (19 patients, 79%), treatment toxicity (2 patients) and non-related (3 patients, 12%). Toxicity profile was good especially when concomitant dexamethasone was administered. In the prophylactic cohort the incidence of CNS relapse in DLBCL group was similar to previously reported for HDMTX and much better than IT MTX. A high number of ITLC injections was associated with better rates of CSF clearance, clinical responses, PFS and lower relapses. Survival is still poor in CNS lymphomatosis and new therapeutic approaches are still needed.


Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Burkitt Lymphoma/drug therapy , Central Nervous System Neoplasms/drug therapy , Cytarabine/therapeutic use , Liposomes , Adolescent , Adult , Aged , Aged, 80 and over , Antimetabolites, Antineoplastic/adverse effects , Burkitt Lymphoma/prevention & control , Central Nervous System Neoplasms/prevention & control , Child , Cytarabine/adverse effects , Female , Humans , Injections, Spinal , Male , Middle Aged , Survival Analysis , Young Adult
14.
Leuk Res ; 41: 12-20, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26686475

ABSTRACT

BACKGROUND AND OBJECTIVE: The prognosis of acute lymphoblastic leukemia (ALL) is poor in older adults and elderly patients, and subtype-oriented prospective trials are scarce in these patients. We present the results of three prospective parallel subtype-oriented protocols in fit patients older than 55 years. PATIENTS AND METHODS: In 2008, three prospective phase II trials in patients older than 55 years were activated: ALLOLD07 for Philadephia (Ph) chromosome-negative ALL, ALLOPH07 for Ph-positive ALL, and BURKIMAB08 for mature B-ALL. Early death (ED), complete remission (CR), disease-free survival (DFS), overall survival (OS) and toxicity were analyzed. RESULTS: 56, 53 and 21 patients from the ALLOLD07, ALLOPH07 and BURKIMAB08 trials, respectively, were evaluable. CR was 74%, 87% and 70%, with an ED rate of 13%, 11% and 15%, respectively. The medians of DFS were 8 and 38 months for ALLOLD07 and ALLOPH07 protocols, not being achieved in the BURKIMAB08 trial (p=0.001), and the median OS was 12, 37 and 25 months, respectively (p=0.030). Neutropenia, thrombocytopenia and infections were less frequent in the ALLOPH07 trial vs. ALLOLD07 and BURKIMAB trials, and renal toxicity and mucositis were more frequent in the BURKIMAB08 trial vs. the ALLOLD07 and ALLOPH07 trials. ECOG score and WBC count had prognostic significance for OS in ALLOPH07 and BURKIMAB08 trials, whereas no prognostic factors were identified in ALLOLD07 protocol. CONCLUSION: Subtype-oriented treatment had an impact in the outcome of older adults with ALL. The poorest outcome was observed in Ph-negative non-Mature B-cell ALL patients, for whom improvements in therapy are clearly needed.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Aged , Aged, 80 and over , Feasibility Studies , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Prognosis
15.
J Clin Oncol ; 32(15): 1595-604, 2014 May 20.
Article in English | MEDLINE | ID: mdl-24752047

ABSTRACT

PURPOSE: 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 AND METHODS: 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). RESULTS: 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. CONCLUSION: 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.


Subject(s)
Consolidation Chemotherapy , Flow Cytometry , Philadelphia Chromosome , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Adolescent , Adult , Age Factors , Consolidation Chemotherapy/adverse effects , Consolidation Chemotherapy/mortality , Disease-Free Survival , Female , Genetic Predisposition to Disease , Hematopoietic Stem Cell Transplantation , Humans , Kaplan-Meier Estimate , Logistic Models , Maintenance Chemotherapy , Male , Middle Aged , Multivariate Analysis , Neoplasm, Residual , Patient Selection , Phenotype , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Predictive Value of Tests , Proportional Hazards Models , Risk Factors , Spain , Time Factors , Treatment Outcome , Young Adult
16.
Blood ; 123(12): 1864-9, 2014 Mar 20.
Article in English | MEDLINE | ID: mdl-24501214

ABSTRACT

Flow cytometry (FCM) is more sensitive than conventional cytology for detection of occult leptomeningeal lymphoma; however, some FCM-negative patients show central nervous system (CNS) recurrence. Here, we evaluated the cerebrospinal fluid (CSF) levels of 13 B-cell-associated markers and their contribution to the diagnosis of CNS lymphoma in 91 diffuse large B-cell lymphomas (DLBCL) and 22 Burkitt lymphomas (BLs). From all markers tested, CD19 was the most informative. Thus, higher soluble CD19 (sCD19) levels were associated with a greater frequency of neurological symptoms in DLBCL and BL and with parenchymal CNS lymphoma in DLBCL; sCD19 emerged as a powerful predictor of event-free and overall survival in DLBCL and BL, particularly when combined with FCM detection of CNS disease. These results support the utility of combined FCM detection of lymphoma cells and assessment of sCD19 levels in CSF, for more accurate identification of CNS disease in DLBCL and BL patients.


Subject(s)
Antigens, CD19/cerebrospinal fluid , Biomarkers, Tumor/cerebrospinal fluid , Burkitt Lymphoma/immunology , Central Nervous System Neoplasms/immunology , Lymphoma, Large B-Cell, Diffuse/immunology , Adult , Aged , Burkitt Lymphoma/cerebrospinal fluid , Burkitt Lymphoma/diagnosis , Central Nervous System Neoplasms/cerebrospinal fluid , Central Nervous System Neoplasms/diagnosis , Disease-Free Survival , Female , Flow Cytometry , Humans , Kaplan-Meier Estimate , Lymphoma, Large B-Cell, Diffuse/cerebrospinal fluid , Lymphoma, Large B-Cell, Diffuse/diagnosis , Male , Middle Aged , Prognosis , Solubility
18.
Blood Coagul Fibrinolysis ; 21(2): 188-91, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20040859

ABSTRACT

Acquired hemophilia A is a rare disorder characterized by the presence of an autoantibody (mainly immunoglobulin G) to the clotting factor VIII with a clinical resemblance to hemophilia A. This autoantibody may arise because of dysregulation of the immune system. It is associated with various autoimmune or dermatologic diseases, pregnancy, or drug ingestion, but in almost 50% patients, the cause is unknown. In the present study, we have reported three different clinical presentations of acquired hemophilia. In two cases, the underlying disorder was the probable respiratory chronic disease (asthma), and in the other, it was idiopathic. We reviewed the response to a given treatment. The severity of the clinical presentation was different in all the cases, and was taken into account when we decided on the best course of treatment. The present report presents two patients successfully treated with a tapering course of steroids, and one with the anti-CD20 monoclonal antibody not given as first line treatment.


Subject(s)
Asthenia/complications , Asthma/complications , Hematoma/complications , Hemophilia A/etiology , Aged , Asthenia/drug therapy , Asthma/drug therapy , Factor VIIa/therapeutic use , Female , Hematoma/surgery , Hemophilia A/drug therapy , Humans , Male , Middle Aged , Recombinant Proteins/therapeutic use , Shock, Hemorrhagic/drug therapy , Steroids/therapeutic use
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