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2.
Front Oncol ; 14: 1385987, 2024.
Article in English | MEDLINE | ID: mdl-39011475

ABSTRACT

Introduction: Chronic myelomonocytic leukemia (CMML) and myelodysplastic syndromes (MDS) with ring sideroblasts (RS) or SF3B1 mutation (MDS-RS/SF3B1) differ in many clinical features, but share others, such as anemia. RS and SF3B1 mutation can also be found in CMML. Methods: We compared CMML with and without RS/SF3B1 and MDS-RS/SF3B1 considering the criteria established by the 2022 World Health Organization classification. Results: A total of 815 patients were included (CMML, n=319, CMML-RS/SF3B1, n=172 and MDS-RS/SF3B1, n=324). The percentage of RS was ≥15% in almost all CMML-RS/SF3B1 patients (169, 98.3%) and most (125, 72.7%) showed peripheral blood monocyte counts between 0.5 and 0.9 x109/L and low risk prognostic categories. CMML-RS/SF3B1 differed significantly from classical CMML in the main clinical characteristics, whereas it resembled MDS-RS/SF3B1. At a molecular level, CMML and CMML-RS/SF3B1 had a significantly higher frequency of mutations in TET2 (mostly multi-hit) and ASXL1 (p=0.013) and CMML had a significantly lower frequency of DNMT3A and SF3B1 mutations compared to CMML/MDS-RS/SF3B1. Differences in the median overall survival among the three groups were statistically significant: 6.75 years (95% confidence interval [CI] 5.41-8.09) for CMML-RS/SF3B1 vs. 3.17 years (95% CI 2.56-3.79) for CMML vs. 16.47 years (NA) for MDS-RS/SF3B1, p<0.001. Regarding patients with CMML and MDS, both with SF3B1 mutation, survival did not significantly differ. CMML had a higher risk of transformation to acute myeloid leukemia (24% at 8 years, 95%CI 19%-30%). Discussion: CMML-RS/SF3B1 mutation resembles MDS-RS/SF3B1 in terms of phenotype and clearly differs from CMML. The presence of ≥15% RS and/or SF3B1 in CMML is associated with a low monocyte count. SF3B1 mutation clearly improves the prognosis of CMML.

5.
J Clin Med ; 13(3)2024 Jan 29.
Article in English | MEDLINE | ID: mdl-38337473

ABSTRACT

e13a2 and e14a2 are the most frequent transcript types of the BCR::ABL1 fusion gene in chronic myeloid leukemia (CML). The current goal with tyrosine kinase inhibitors (TKI) is to achieve sustained deep molecular response (DMR) in order to discontinue TKI treatment and remain in the so-called treatment-free remission (TFR) phase, but biological factors associated with these goals are not well established. This study aimed to determine the effect of transcript type on TFR in patients receiving frontline treatment with imatinib (IM) or second-generation TKI (2G-TKI). Patients treated at least 119 months with IM presented less post-discontinuation relapse than those that discontinued IM before 119 months (p = 0.005). In addition, cases with the e14a2 transcript type treated at least 119 months with IM presented a better TFR (p = 0.024). On the other hand, the type of transcript did not affect the cytogenetic or molecular response in 2G-TKI treated patients; however, the use of 2G-TKI may be associated with higher and earlier DMR in patients with the e14a2 transcript.

6.
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
7.
Blood Adv ; 8(5): 1155-1166, 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38113467

ABSTRACT

ABSTRACT: Risk stratification is crucial to the successful treatment of acute lymphoblastic leukemia (ALL). Although numerous risk factors have been identified, an optimal prognostic model for integrating variables has not been developed. We used individual patient data from 4 contemporary academic national clinical trials, UKALL14, NILG-ALL10/07, GIMEMA-LAL1913, and PETHEMA-ALL-HR2011, to generate and validate the European Working Group for Adult ALL prognostic index (EWALL-PI), which is based on white blood cell count, genetics, and end of induction minimal residual disease (MRD). Individual patient risk scores were calculated for 778 patients aged 15 to 67 years in complete remission using the validated UKALL-PI formula, applying minor modifications to reflect differences between pediatric and adult ALL. Per-trial analysis revealed that EWALL-PI correlated with relapse and death. Regression analysis revealed that each unit increase in EWALL-PI increased the risk of relapse or death by ∼30% with no evidence of heterogeneity across trials or patient subgroups. EWALL-PI-defined risk models outperformed the stratification algorithms used by each trial. Threshold analysis revealed an EWALL-PI threshold that divided patients with B cell and T cell into standard (EWALL-PI <2.50) and high (EWALL-PI ≥2.50) risk groups, respectively. Per-trial analysis showed that patients at high risk had a significantly increased relapse rate and inferior survival compared with patients with standard risk (subdistribution hazard ratio for relapse, ranged from 1.85 to 3.28; hazard ratio for death, 1.73 to 3.03). Subgroup analysis confirmed the robustness of these risk groups by sex, age, white blood cell count, and lineage. In conclusion, we validated an integrated risk model across 4 independent adult ALL clinical trials, demonstrating its utility defining clinically relevant risk groups.


Subject(s)
Precursor Cell Lymphoblastic Leukemia-Lymphoma , Adult , Humans , Child , Prognosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Algorithms , Risk Factors , Recurrence
8.
Eur J Haematol ; 111(3): 485-490, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37381686

ABSTRACT

INTRODUCTION: The prognosis of relapsed B cell precursor acute lymphoblastic leukemia (B-ALL) is poor and few patients can be successfully rescued with conventional therapies. Inotuzumab ozogamicin (IO), an antibody against the CD22 antigen linked to calicheamicin, has been approved as a rescue treatment in relapsed/refractory (R/R) B-ALL. PATIENTS AND METHODS: This was an observational, retrospective, multicenter study of adult patients included in the Spanish program of compassionate use of IO in centers from the PETHEMA group (Programa Español de Tratamientos en Hematología). RESULTS: Thirty-four patients with a median age of 43 years (range, 19-73) were included. Twenty patients (59%) were refractory to the last treatment, IO treatment was given as ≥3rd salvage treatment in 25 patients (73%) and 20 patients (59%) received allogeneic hematopoietic stem cell transplantation before IO treatment. After a median of 2 cycles of IO, 64% of patients achieved complete response (CR)/complete response with incomplete recovery. The median response duration, progression-free survival and overall survival (OS) were 4.7 (95%CI, 2.4-7.0 months), 3.5 (95%CI, 1.0-5.0 months) and 4 months (95%CI, 1.9-6.1 months) respectively, with better OS for patients with relapsed B-ALL versus refractory disease (10.4 vs. 2.5 months, respectively) (p = .01). There was a trend for better OS for patients with first CR duration >12 months (7.2 months [95%CI, 3.2-11.2] vs. 3 months [95% CI, 1.8-4.2] respectively) (p = .054). There was no sinusoidal obstruction syndrome (SOS) event during IO treatment, but three patients (9%) developed grade 3-4 SOS during alloHSCT after IO treatment. CONCLUSIONS: Our study showed slightly inferior outcomes of the pivotal trial probably due to poorer risk factors and late onset of IO therapy of recruited patients. Our results support early use of IO in relapsed/refractory ALL patients.


Subject(s)
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Humans , Adult , Young Adult , Middle Aged , Aged , Inotuzumab Ozogamicin/adverse effects , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Spain/epidemiology , Retrospective Studies , Antibodies, Monoclonal, Humanized
10.
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
11.
Sci Rep ; 12(1): 13057, 2022 07 29.
Article in English | MEDLINE | ID: mdl-35906470

ABSTRACT

The screening of the BCR::ABL1 kinase domain (KD) mutation has become a routine analysis in case of warning/failure for chronic myeloid leukemia (CML) and B-cell precursor acute lymphoblastic leukemia (ALL) Philadelphia (Ph)-positive patients. In this study, we present a novel DNA-based next-generation sequencing (NGS) methodology for KD ABL1 mutation detection and monitoring with a 1.0E-4 sensitivity. This approach was validated with a well-stablished RNA-based nested NGS method. The correlation of both techniques for the quantification of ABL1 mutations was high (Pearson r = 0.858, p < 0.001), offering DNA-DeepNGS a sensitivity of 92% and specificity of 82%. The clinical impact was studied in a cohort of 129 patients (n = 67 for CML and n = 62 for B-ALL patients). A total of 162 samples (n = 86 CML and n = 76 B-ALL) were studied. Of them, 27 out of 86 harbored mutations (6 in warning and 21 in failure) for CML, and 13 out of 76 (2 diagnostic and 11 relapse samples) did in B-ALL patients. In addition, in four cases were detected mutation despite BCR::ABL1 < 1%. In conclusion, we were able to detect KD ABL1 mutations with a 1.0E-4 sensitivity by NGS using DNA as starting material even in patients with low levels of disease.


Subject(s)
Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Precursor Cell Lymphoblastic Leukemia-Lymphoma , DNA , Drug Resistance, Neoplasm , Fusion Proteins, bcr-abl/genetics , Genomics , High-Throughput Nucleotide Sequencing/methods , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Mutation , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Protein Kinase Inhibitors/pharmacology
12.
Blood ; 140(1): 38-44, 2022 07 07.
Article in English | MEDLINE | ID: mdl-35421218

ABSTRACT

CD19-directed immunotherapies have revolutionized the treatment of advanced B-cell acute lymphoblastic leukemia (B-ALL). Despite initial impressive rates of complete remission (CR) many patients ultimately relapse. Patients with B-ALL successfully treated with CD19-directed T cells eventually relapse, which, coupled with the early onset of CD22 expression during B-cell development, suggests that preexisting CD34+CD22+CD19- (pre)-leukemic cells represent an "early progenitor origin-related" mechanism underlying phenotypic escape to CD19-directed immunotherapies. We demonstrate that CD22 expression precedes CD19 expression during B-cell development. CD34+CD19-CD22+ cells are found in diagnostic and relapsed bone marrow samples of ∼70% of patients with B-ALL, and their frequency increases twofold in patients with B-ALL in CR after CD19 CAR T-cell therapy. The median of CD34+CD19-CD22+ cells before treatment was threefold higher in patients in whom B-ALL relapsed after CD19-directed immunotherapy (median follow-up, 24 months). Fluorescence in situ hybridization analysis in flow-sorted cell populations and xenograft modeling revealed that CD34+CD19-CD22+ cells harbor the genetic abnormalities present at diagnosis and initiate leukemogenesis in vivo. Our data suggest that preleukemic CD34+CD19-CD22+ progenitors underlie phenotypic escape after CD19-directed immunotherapies and reinforce ongoing clinical studies aimed at CD19/CD22 dual targeting as a strategy for reducing CD19- relapses. The implementation of CD34/CD19/CD22 immunophenotyping in clinical laboratories for initial diagnosis and subsequent monitoring of patients with B-ALL during CD19-targeted therapy is encouraged.


Subject(s)
Antigens, CD19 , Burkitt Lymphoma , Antigens, CD34 , B-Lymphocytes , Humans , Immunophenotyping , In Situ Hybridization, Fluorescence , Recurrence , Sialic Acid Binding Ig-like Lectin 2
13.
Br J Haematol ; 196(3): 670-675, 2022 02.
Article in English | MEDLINE | ID: mdl-34549416

ABSTRACT

The prognosis of t(1;19)(q23;p13)/transcription factor 3-pre-B-cell leukaemia homeobox 1 (TCF3-PBX1) in adolescent and adult patients with acute lymphoblastic leukaemia (ALL) treated with measurable residual disease (MRD)-oriented trials remains controversial. In the present study, we analysed the outcome of adolescent and adult patients with t(1;19)(q23;p13) enrolled in paediatric-inspired trials. The patients with TCF3-PBX1 showed similar MRD clearance and did not have different survival compared with other B-cell precursor ALL patients. However, patients with TCF3-PBX1 had a significantly higher cumulative incidence of relapse, especially among patients aged ≥35 years carrying additional cytogenetic alterations. These patients might benefit from additional/intensified therapy (e.g. immunotherapy in first complete remission with or without subsequent haematopoietic stem cell transplantation).


Subject(s)
Chromosomes, Human, Pair 19 , Chromosomes, Human, Pair 1 , Neoplasm, Residual/therapy , Oncogene Proteins, Fusion/genetics , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/therapy , Translocation, Genetic , Adolescent , Adult , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chromosome Banding , Disease Management , Female , Humans , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Staging , Neoplasm, Residual/diagnosis , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/mortality , Prognosis , Remission Induction , Treatment Outcome , Young Adult
14.
Med. clín (Ed. impr.) ; 157(8): 380-384, octubre 2021. tab, graf
Article in Spanish | IBECS | ID: ibc-215556

ABSTRACT

Fundamento y objetivo: La enfermedad del injerto contra el receptor (EICR) y las infecciones son complicaciones del trasplante alogénico de progenitores hematopoyéticos (alo-TPH). La globulina antitimocítica (ATG) es una estrategia empleada para la profilaxis de la EICR. Este estudio analiza los resultados y la frecuencia de infecciones en función del uso de ATG, después de un alo-TPH de donante no emparentado (DNE) en pacientes con leucemia aguda y síndrome mielodisplásico.Pacientes y métodoEstudio retrospectivo de pacientes que recibieron un alo-TPH de DNE entre diciembre de 2007 y abril de 2019. Se compararon los principales resultados en función del uso de ATG.ResultadosSe incluyó a 66 pacientes. No se encontraron diferencias significativas en el grupo ATG (n=50) frente al no ATG (n=16) en supervivencia global, incidencia acumulada de recaída, mortalidad no debida a recaída o incidencia acumulada de EICR aguda o crónica. Hubo mayor frecuencia de infecciones en el grupo ATG (60 frente a 19%; p=0,004).ConclusionesEn este estudio no se demostró diferencia en los principales resultados del alo-TPH en función del uso de ATG, pero hubo más infecciones en el grupo que recibió ATG. (AU)


Background and purpose: Graft-versus-host disease (GVHD) and infections are complications after allogeneic stem cell transplantation (alloSCT). Anti-thymocyte globulin (ATG) is a strategy used as prophylaxis for GVHD. The study analyses the outcomes and frequency of infections with or without ATG after an unrelated donor alloSCT in patients with acute leukaemia and myelodysplastic syndrome.Patients and methodsRetrospective study of patients receiving an unrelated donor alloSCT between December 2007 and April 2019. The main outcomes were analysed according to use or not of ATG.ResultsSixty-six patients were included. No significant differences were found between the ATG group (n=50) vs. no-ATG group (n=16) in overall survival, cumulative incidence of relapse, cumulative incidence of non-relapse mortality or cumulative incidence of acute GVHD or chronic GVHD. There was a greater frequency of infections in the ATG group (60 vs. 19%, P=.004).ConclusionsIn this study, no differences were shown in the main outcomes of alloSCT based on the use of ATG, although more infections were documented in the ATG group. (AU)


Subject(s)
Humans , Antilymphocyte Serum/therapeutic use , Hematopoietic Stem Cell Transplantation/adverse effects , Leukemia, Myeloid, Acute/complications , Leukemia, Myeloid, Acute/therapy , Myelodysplastic Syndromes/complications , Myelodysplastic Syndromes/therapy , Transplantation, Homologous , Unrelated Donors
15.
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
16.
Clin Lymphoma Myeloma Leuk ; 21(10): e801-e809, 2021 10.
Article in English | MEDLINE | ID: mdl-34376375

ABSTRACT

BACKGROUND AND OBJECTIVE: SARS-CoV-2 infection has bimodal distribution in Europe with a first wave in March to June 2020 and a second in September 2020 to February 2021. We compared the frequency, clinical characteristics and outcomes of adults with acute lymphoblastic leukemia (ALL) and infection in the first vs. second pandemic waves in Spain. PATIENTS AND METHODS: In this prospective study the characteristics of ALL and COVID-19 infection, comorbidities, treatment and outcome in the two periods were compared. The study ended when vaccination against SARS-CoV-2 was implemented in Spain. RESULTS: Twenty eight patients were collected in the first wave and 24 in the second. The median age was 46.5 years (range 20-83). Patients from the first wave had a trend to more severe ALL (higher frequency of patients under induction or submitted to transplantation or under immunosuppressive therapy). No significant differences were observed in need for oxygen support, intensive care unit (ICU) requirement, days in ICU and time to COVID-19 infection recovery. Seventeen patients (33%) died, with death attributed to COVID infection in 15 (29%), without significant differences in the 100 day overall survival (OS) probabilities in the two waves (68% ± 17% vs. 56% ± 30%). The only prognostic factor for OS identified by was the presence of comorbidities at COVID-19 infection (HR: 5.358 [95% CI: 1.875- 15.313]). CONCLUSION: The frequency and mortality of COVID-19 infection were high in adults with ALL, without changes over time, providing evidence in favor of vaccination priority for these patients.


Subject(s)
COVID-19/epidemiology , Intensive Care Units/statistics & numerical data , Outcome Assessment, Health Care/statistics & numerical data , Precursor Cell Lymphoblastic Leukemia-Lymphoma/epidemiology , Adult , Aged , Aged, 80 and over , COVID-19/therapy , COVID-19/virology , Comorbidity , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Multivariate Analysis , Outcome Assessment, Health Care/methods , Pandemics/prevention & control , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Prospective Studies , SARS-CoV-2/physiology , Spain/epidemiology , Young Adult
17.
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
18.
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
19.
Med Clin (Barc) ; 157(8): 380-384, 2021 Oct 22.
Article in English, Spanish | MEDLINE | ID: mdl-33160624

ABSTRACT

BACKGROUND AND PURPOSE: Graft-versus-host disease (GVHD) and infections are complications after allogeneic stem cell transplantation (alloSCT). Anti-thymocyte globulin (ATG) is a strategy used as prophylaxis for GVHD. The study analyses the outcomes and frequency of infections with or without ATG after an unrelated donor alloSCT in patients with acute leukaemia and myelodysplastic syndrome. PATIENTS AND METHODS: Retrospective study of patients receiving an unrelated donor alloSCT between December 2007 and April 2019. The main outcomes were analysed according to use or not of ATG. RESULTS: Sixty-six patients were included. No significant differences were found between the ATG group (n=50) vs. no-ATG group (n=16) in overall survival, cumulative incidence of relapse, cumulative incidence of non-relapse mortality or cumulative incidence of acute GVHD or chronic GVHD. There was a greater frequency of infections in the ATG group (60 vs. 19%, P=.004). CONCLUSIONS: In this study, no differences were shown in the main outcomes of alloSCT based on the use of ATG, although more infections were documented in the ATG group.


Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Myelodysplastic Syndromes , Antilymphocyte Serum/therapeutic use , Graft vs Host Disease/etiology , Graft vs Host Disease/prevention & control , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Leukemia, Myeloid, Acute/complications , Leukemia, Myeloid, Acute/therapy , Myelodysplastic Syndromes/complications , Myelodysplastic Syndromes/therapy , Neoplasm Recurrence, Local , Retrospective Studies , Stem Cell Transplantation , Transplantation Conditioning , Transplantation, Homologous , Unrelated Donors
20.
Med. clín (Ed. impr.) ; 155(9): 382-387, nov. 2020. tab, graf
Article in English | IBECS | ID: ibc-198320

ABSTRACT

INTRODUCTION: The impact of an admission to ICU before stem cell transplantation (SCT) on post-SCT outcome is not well established. PATIENTS AND METHODS: We reviewed the medical records of patients who had received a first SCT between 2000 and 2016 in our institution. The outcome of 22 patients who required ICU admission during chemotherapy prior to SCT (ICU group) was compared with 44 matched patients (1:2) who did not need it (NO-ICU group). RESULTS: There were no differences in transplant complications, in time to neutrophil and platelet recovery or in the length of hospital stay during SCT between the ICU and NO-ICU groups. However, microbiologically documented infections were more common in the ICU group (16/20) than in the NO-ICU group (18/39) (p=.027). The 5-yr overall survival probability (CI 95%) was 49% (28-70%) in the ICU vs. 45% (29-61%) in the NO-ICU group (p=.353), while the 5-yr incidence of non-relapse mortality was 32% (14-52%) and 24% (12-38%) (p=.333), respectively. Six patients (27%) in the ICU group and 8 (18%) in the NO-ICU group required admission to the ICU during or after the SCT procedure (p=.293). Twelve (54%) patients in the ICU and 22 (50%) in the NO-ICU group died, the causes of death were similar in both groups. CONCLUSION: Our results show that admission to the ICU prior to SCT does not have a negative impact on patient outcomes following SCT and should not be considered as an exclusion criterion for SCT


INTRODUCCIÓN: No se conoce con exactitud el impacto de la necesidad de ingreso previo en una unidad de cuidados intensivos (UCI) en la supervivencia postrasplante de progenitores hematopoyéticos (TPH). PACIENTES Y MÉTODOS: Se revisaron los archivos de pacientes que habían recibido un TPH entre el 2000 y 2016 en una única institución. El resultado del TPH en 22 pacientes que habían precisado de ingreso en una UCI durante las quimioterapias administradas previas al TPH (grupo UCI) se comparó con el de 44 pacientes controles (1:2) trasplantados que no habían precisado ingreso previo en UCI (grupo NO-UCI). RESULTADOS: No hallamos diferencias en las complicaciones post-TPH, en el tiempo de injerto de neutrófilos o de plaquetas, ni tampoco en la duración del ingreso hospitalario entre el grupo UCI y el grupo NO-UCI (p = 0,353). Sin embargo, la incidencia de infecciones documentadas microbiológicamente fue mayor en el grupo UCI (16/20) que en el NO-UCI. La probabilidad de supervivencia a 5 años (IC95%) fue del 49% (28-70%) para el grupo UCI vs. el 45% (29-61%) para el grupo NO-UCI (p = 0,353), mientras que la mortalidad relacionada con el TPH a los 5 años fue del 32% (14-52%) y 24% (12-38%) (p = 0,333), respectivamente. Seis pacientes (27%) en el grupo UCI y 8 (18%) en el grupo NO-UCI precisaron ingreso en UCI durante o después del proceso de TPH (p = 0,293). Doce pacientes (54%) en el grupo UCI y 22 (50%) en el NO-UCI fallecieron, y las causas de muerte fueron similares en ambos grupos. CONCLUSIÓN: El ingreso en UCI no tiene necesariamente un impacto negativo en los resultados de un TPH posterior en pacientes hematológicos y no debería ser criterio de exclusión para dicho procedimiento


Subject(s)
Humans , Male , Female , Adult , Intensive Care Units/statistics & numerical data , Hospitalization/statistics & numerical data , Hematopoietic Stem Cell Transplantation/adverse effects , Critical Care , Stem Cell Transplantation/statistics & numerical data , Hematopoietic Stem Cell Transplantation/statistics & numerical data , Postoperative Care/statistics & numerical data , Survivorship , Case-Control Studies , Hematopoietic Stem Cell Transplantation/mortality , Length of Stay/statistics & numerical data
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