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2.
Blood Adv ; 5(17): 3436-3444, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34461632

RESUMO

The expression of CD20 in precursor B-cell acute lymphoblastic leukemia (B-ALL) is associated with poor outcomes. The addition of rituximab to intensive chemotherapy in CD20+ ALL has led to improved outcomes in several studies. However, there is no clear evidence regarding the optimal number of doses and its benefit without an allogeneic stem cell transplant. Achieving measurable residual disease (MRD)-negative status postinduction would reduce the requirement for a transplant. Novel approaches are needed to induce a higher proportion of MRD-negative complete remission in patients with high-risk ALL. Given bortezomib's activity in relapsed ALL and its synergism with rituximab in B-cell lymphomas, the addition of bortezomib to rituximab and chemotherapy may provide an incremental benefit in CD20+ precursor B-ALL. We conducted a phase 2 study to test the activity of bortezomib and rituximab in combination with a pediatric-inspired regimen during induction therapy in newly diagnosed adolescents and adults (aged >14 years) with CD20+, Philadelphia-negative precursor B-ALL; bone marrow MRD negativity at the end of induction was the primary end point. From December 2017 through August 2019, a total of 35 patients were enrolled. End-of-induction MRD-negative status was achieved in 70.9% of patients, as opposed to 51.7% in the historical cohort treated with chemotherapy alone. MRD-negative rates improved to 87.5% post-consolidation. At a median follow-up of 21 months, event-free survival and overall survival rates were 78.8% (95% confidence interval, 66-94) and 78.7% (95% confidence interval, 65.8-94), respectively. There was no significant increase in toxicity with bortezomib and rituximab compared with the historical cohort. The incidence of neuropathy was 26% (all less than grade 3). The combination of bortezomib, rituximab, and a pediatric-inspired ALL regimen was active and well tolerated in de novo CD20+ Philadelphia-negative precursor B-ALL. This trial was registered with the Clinical Trials Registry-India as CTRI/2017/04/008393(http://ctri.nic.in/Clinicaltrials).

3.
Indian J Med Res ; 153(4): 475-483, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34380794

RESUMO

Background & objectives: B-cell chronic lymphocytic leukaemia (B-CLL) is one of the most common forms of adult leukaemia, with a highly variable clinical course. Specific chromosomal and genetic aberrations are used clinically to predict prognosis, independent from conventional clinical markers. Molecular cytogenetic methods such as fluorescence in situ hybridization (FISH) detect aberrations in up to 80 per cent B-CLL patients. This study was conducted to score the frequencies of recurrent aberrations, i.e., del(13q14), trisomy 12, del(11q22), del(17p13), del(6q21) and IgH (immunoglobulin heavy chain) translocations and to understand their role in prognostication and risk stratification. Methods: FISH studies were performed on bone marrow aspirate or peripheral blood of 280 patients using commercially available disease-specific probe set. The data were correlated with clinical and haematological parameters such as low haemoglobin, splenomegaly and lymphadenopathy. Results: Chromosomal aberrations were detected in 79 per cent of patients, with del(13q14) (57%) as the most common cytogenetic aberration, followed by trisomy 12 (27%), del(11q22) (22%), t(14q32) (19%), del(17p13) (18%) and del(6q21) (9%). Single or in coexistence with other aberration del(13q14) had a favourable outcome in comparison to del(11q22), t(14q32), del(17p13) and del(6q21) which were associated with advanced stages of the disease. Trisomy 12 had a variable clinical course. Interpretation & conclusions: FISH was found to be a sensitive and efficient technique in detecting the prevalence of recurrent cytogenetic abnormalities. Each of these aberrations is an important independent predictor of disease progression and survival which aids in designing risk-adapted treatment strategies for better disease management.


Assuntos
Leucemia Linfocítica Crônica de Células B , Aberrações Cromossômicas , Análise Citogenética , Humanos , Hibridização in Situ Fluorescente , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/genética , Prognóstico
4.
Indian J Pathol Microbiol ; 64(2): 302-309, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33851624

RESUMO

Background and Aim: Multicentric Castleman's disease (MCD) is a rare lymphoproliferative disorder manifesting as multiple lymphadenopathy, multiorgan involvement, and inflammatory symptoms. This study aims at highlighting some unique features of MCD in Indian patients. Materials and Methods: These 17 patients from review of 78 cases of Castleman's disease (CD) diagnosed. Besides routine tissue sections were stained for Human Herpes Virus 8 latency associated nuclear antigen (HHV8-LANA) by immunohistochemistry (IHC) and Epstein Barr virus latent membrane protein (EBV-LMP) or Epstein Barr Virus by in situ hybridization (EBER-ISH). Result: The cases included Plasma cell variant (11 cases), mixed MCD (4 cases) and two concurrent MCD with large B cell lymphoma in HIV positive patients. Median age of disease onset was 47 years and female predominance was seen. Out of 15 MCD uncomplicated by lymphoma, 5 had POEMS (Polyneuropathy, organomegaly, endocrinopathy, myeloma protein, skin changes) and one also had TAFRO (Thrombocytopenia, anasarca, fever, marrow reticulin fibrosis, organomegaly, normal or slightly elevated immunoglobulin) syndrome. Out of 10 MCD without lymphoma, 2 cases showed few EBV positive large cells, both have features of POEMS. All 17 MCD cases were negative for HHV8-LANA IHC. Two HIV patients with MCD had large cell lymphoma, intrasinusoidal pattern, of which one was EBV positive. Though four relapses were seen, none died from disease. One of the two patients complicated by lymphoma died from disease. Conclusion: Indian patients with MCD show female preponderance and are negative for HHV8 but show EBV positive cells. This makes a case for role of EBV in etiopathogenesis of MCD in India.


Assuntos
Hiperplasia do Linfonodo Gigante/diagnóstico , Hiperplasia do Linfonodo Gigante/virologia , Herpesvirus Humano 4/isolamento & purificação , Herpesvirus Humano 8/isolamento & purificação , Adulto , Hiperplasia do Linfonodo Gigante/patologia , Infecções por Vírus Epstein-Barr/complicações , Feminino , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Síndrome POEMS/complicações , Síndrome POEMS/patologia , Plasmócitos/patologia , Estudos Retrospectivos , Centros de Atenção Terciária , Adulto Jovem
5.
Br J Haematol ; 193(1): e1-e4, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33656752
6.
JCO Glob Oncol ; 7: 361-367, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33689483

RESUMO

PURPOSE: The prognosis of relapsed and refractory multiple myeloma (RRMM) that is refractory to bortezomib and lenalidomide is very poor wherein the median survival is between 3 and 9 months. We did this retrospective analysis to study the pattern of utilization, tolerance, and outcomes with pomalidomide in these patients having RRMM. MATERIALS AND METHODS: Retrospective analysis of all the patients who were treated with generic pomalidomide at Tata Memorial Centre, Mumbai, during the period of May 2017 to March 2019 was done. Patients with secretory disease and who had completed at least one cycle of pomalidomide were analyzed for response rates, toxicity, and survival outcomes. RESULTS: A total of 81 patients received pomalidomide-based therapy during this study period, out of which 75 were included in the survival analysis. Forty-eight patients (59.3%) were refractory to both lenalidomide and bortezomib. Overall response rate was 58.7%. Five patients (6.7%) achieved complete response, very good partial response was seen in 13 patients (17.3%), and partial response was seen in 26 patients (34.7%). After a median follow-up of 11 months (range 2-27 months), median progression-free survival was 9.1 months (95% CI, 5.4 to 12.9 months). Median progression-free survival for patients who were refractory to both lenalidomide and bortezomib versus nonrefractory was 5.5 and 12.6 months, respectively, which was significant statistically (P = .04, hazard ratio, 0.35, 95% CI, 0.28 to 0.97). The median overall survival was not reached. Important toxicities included anemia (28%), neutropenia (16%), pneumonia (16%), and venous thrombosis (5%). CONCLUSION: Generic pomalidomide-based therapy is an effective option and is well tolerated in patients with RRMM. Higher response rates and longer survival seen in our study are possibly because of heterogeneity of the study population.


Assuntos
Mieloma Múltiplo , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Dexametasona/uso terapêutico , Humanos , Mieloma Múltiplo/tratamento farmacológico , Estudos Retrospectivos , Atenção Terciária à Saúde , Talidomida/análogos & derivados
7.
Leukemia ; 35(5): 1392-1404, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33558666

RESUMO

We accrued 201 patients of adult AML treated with conventional therapy, in morphological remission, and evaluated MRD using sensitive error-corrected next generation sequencing (NGS-MRD) and multiparameter flow cytometry (FCM-MRD) at the end of induction (PI) and consolidation (PC). Nearly 71% of patients were PI NGS-MRD+ and 40.9% PC NGS-MRD+ (median VAF 0.76%). NGS-MRD+ patients had a significantly higher cumulative incidence of relapse (p = 0.003), inferior overall survival (p = 0.001) and relapse free survival (p < 0.001) as compared to NGS-MRD- patients. NGS-MRD was predictive of inferior outcome in intermediate cytogenetic risk and demonstrated potential in favorable cytogenetic risk AML. PI NGS-MRD- patients had a significantly improved survival as compared to patients who became NGS-MRD- subsequently indicating that kinetics of NGS-MRD clearance was of paramount importance. NGS-MRD identified over 80% of cases identified by flow cytometry at PI time point whereas FCM identified 49.3% identified by NGS. Only a fraction of cases were NGS-MRD- but FCM-MRD+. NGS-MRD provided additional information of the risk of relapse when compared to FCM-MRD. We demonstrate a widely applicable, scalable NGS-MRD approach that is clinically informative and synergistic to FCM-MRD in AML treated with conventional therapies. Maximum clinical utility may be leveraged by combining FCM and NGS-MRD modalities.


Assuntos
Leucemia Mieloide Aguda/genética , Neoplasia Residual/diagnóstico , Neoplasia Residual/genética , Adolescente , Adulto , Progressão da Doença , Feminino , Citometria de Fluxo/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Mutação/genética , Neoplasia Residual/patologia , Recidiva , Adulto Jovem
8.
Blood Adv ; 5(5): 1178-1193, 2021 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-33635331

RESUMO

The use of pediatrics-inspired protocols in adolescent and young adult (AYA) acute lymphoblastic leukemia (ALL) results in superior survival compared with the adult protocols. Pediatrics-inspired protocols carry an increased risk of toxicity and treatment-related mortality in low resource settings, which can offset the potential benefits. We studied the outcomes and prognostic factors in the treatment of AYA ALL with a pediatrics-inspired regimen. We retrieved data regarding demographics, investigations, treatment details, and toxicities from the electronic medical records of patients diagnosed with ALL in the 15- to 25-year-old age group who were initiated on a modified Berlin-Frankfurt-Münster 90 (BFM-90) protocol between January 2013 and December 2016 at the Tata Memorial Centre. A total of 349 patients in the 15- to 25-year-old age group were treated with a modified BFM-90 protocol. The use of this pediatrics-inspired protocol resulted in a 3-year event-free survival (EFS) and overall survival (OS) of 59.4% and 61.8%, respectively. Only 15 patients underwent an allogeneic stem cell transplant. Minimal residual disease (MRD) persistence postinduction emerged as the only factor predictive of poor outcomes. A modified BFM-90 protocol is an effective and safe regimen for AYA ALL with an OS and EFS comparable to the published literature.


Assuntos
Citarabina , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adolescente , Adulto , Criança , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Prognóstico , Transplante de Células-Tronco , Adulto Jovem
9.
Artigo em Inglês | MEDLINE | ID: mdl-33629824

RESUMO

BACKGROUND AND AIM: Molecular mechanism of translocation and outcome in variant chronic myeloid leukaemia (vCML) has been a topic of debate. While several cytogenetic studies suggest a low response to Imatinib Mesylate, others demonstrate a similar disease course in both classical and vCML. Besides, many studies comprehensively also link tyrosine kinase domain (TKD) mutations with aggressive clinical outcome. Thus, we aim to study the molecular mechanism of translocation, identify the third partner chromosomes and comment on the disease course and clinical outcome. METHOD: We cytogenetically characterised 25 vCML cases to determine the third partner chromosome, mechanism of translocation and prognostic outcome. We also compared vCML cases with and without TKD mutation to most appropriately outline the clinical consequence and ascertain the potent cause of unresponsiveness to treatment. RESULTS: Third partner chromosome in variant translocation was defined by conventional and molecular cytogenetics. Although in our study most cases showed inadequate clinical response attributable to TKD mutation rather than variant translocation, we observed an inferior outcome in cases involving chromosome 5 as the third partner. CONCLUSION: Thus, we conclude that characterising and reporting new cases of variant translocations, involving various different chromosomes as third partner (with different breakpoints) by cytogenetics, will lead to a better understanding of the disease. To the best of our knowledge, this kind of delineate study has not been applied to precisely comment on the prospects of cytogenetically characterised vCML.

10.
Bone Marrow Transplant ; 56(7): 1558-1562, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33514924

RESUMO

Transplant associated thrombotic microangiopathy (TA-TMA) is life-threatening complication post allogeneic stem cell transplant (ASCT). Risk factors and prognosis of TA-TMA are not well defined. We retrospectively studied consecutive ASCT patients with AML, ALL, and CML from January 2008 to March 2019 to study the incidence, risk factors, and outcomes of TMA. Definitive and probable TA-TMA was defined using Blood and Marrow Transplant Clinical Trials Network (BMT-CTN) and Cho criteria, respectively. Risk factors explored were age, gender, diagnosis, type of transplant, use of tyrosine kinase inhibitors (TKI) pre transplant, conditioning regimen, and acute GVHD. Standard statistical methods were used. Total 241 patients, 179 (74.2 %) males, median age of 29 years were studied. Diagnoses were AML in 104, ALL in 85 (Ph+ve 23) and CML 52. Total 26 (10.7%) patients (22 males) developed TA-TMA at median of day+102. On multivariate analysis, pre-HSCT TKI (OR 2.7, p = 0.028), haplo-HSCT (OR 3.16, p = 0.018) and presence of acute GVHD (OR 4.17, p = 0.003) were significant risk factors. With a median follow up of 60 months, median OS with and without TA-TMA was 18 and 97 months respectively (p = 0.021). The association of pre-HSCT with TKI with TA-TMA merits further exploration in prospective studies.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Microangiopatias Trombóticas , Adulto , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Incidência , Masculino , Estudos Prospectivos , Inibidores de Proteínas Quinases/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Microangiopatias Trombóticas/epidemiologia , Microangiopatias Trombóticas/etiologia
11.
Int J Lab Hematol ; 43(5): 990-999, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33432783

RESUMO

INTRODUCTION: Many new markers are being evaluated to increase the sensitivity and applicability of multicolor flow cytometry (MFC)-based measurable residual disease (MRD) monitoring. However, most of the studies are limited to childhood B-cell lymphoblastic leukemia/lymphoma (B-ALL), and reports in adult B-ALL are extremely scarce and limited to small cohorts. We studied the expression of CD304/neuropilin-1 in a large cohort of adult B-ALL patients and evaluated its practical utility in MFC-based MRD analysis. METHODS: CD304 was studied in blasts from adult B-ALL patients and normal precursor B cells (NPBC) from non-B-ALL bone marrow samples using MFC. CD304 expression intensity and pattern were studied with normalized-mean fluorescent intensity (nMFI) and coefficient of variation of immunofluorescence (CVIF), respectively. MFC-based MRD was performed at end of induction (EOI; day-35), end of consolidation (EOC; day 78-80), and subsequent follow-up (SFU) time points. RESULTS: CD304 was positive in 120/214(56.07%) and was significantly associated with BCR-ABL1 fusion (P = .001). EOI-MRD and EOC-MRD were positive in 129/214(60.3%) and 50/81(61.72%), respectively. CD304 was positive in a significant percentage of EOI (48%, 62/129) and EOC (52%, 26/50) MRD-positive B-ALL samples. Its expression was retained, lost, and gained in 73.7%, 26.3%, and 11.3% of EOI-MRD and 85.7%, 14.3%, and none of EOC-MRD samples, respectively. Low-level MRD (<0.01%) was detectable in 34 of all (EOI + EOC + SFU = 189) MRD-positive samples, and CD304 was found useful in 50% of these samples. CONCLUSION: CD304 is commonly expressed in adult B-ALL and clearly distinguish B-ALL blasts from normal precursor B cells. It is a stable MRD marker and distinctly useful in the detection of MFC-based MRD monitoring, especially in high-sensitivity MRD assay.

12.
Clin Lymphoma Myeloma Leuk ; 21(1): e85-e98, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33189603

RESUMO

BACKGROUND: In the present systematic literature review, we sought to describe the burden and treatment practices of adult acute lymphoblastic leukemia (ALL) in India, which reflect the realities and outcomes in a middle-income country. MATERIALS AND METHODS: We conducted a search for reported studies using terms such as "adult ALL," "epidemiology," and "treatment" in the Medline, Embase, Cochrane, and other database sources. We obtained 249 articles and 18 conference abstracts reported until December 2019. A total of 40 studies were selected to qualitatively summarize the data. RESULTS: The proportion of ALL among adult patients diagnosed with acute leukemia at reporting institutions from 16 Indian studies ranged from 7.3% to 57.8%. Most studies were performed in Northern India (n = 12), had a male preponderance (range, 57%-80%), and had a predominance of B-ALL (range, 65.2%-75.9%). The treatment protocols used for ALL included MCP-841, BFM (Berlin-Frankfurt-Münster)-90, chemotherapy plus a tyrosine kinase inhibitor, GMALL (German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia), and hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone). The complete remission rates and median overall survival for these protocols ranged from 46.7% to 91.4% and 7 to 46 months, respectively. The overall relapse rates were 24.3% to 57.1% within median time of 9 to 24 months, with bone marrow the most frequent relapse site. After relapse, most patients had chosen palliative therapy (range, 78.7%-96.0%). The major treatment-related toxicities included neutropenia, myelosuppression, and infection. CONCLUSIONS: The results from Indian studies on adult ALL are heterogeneous, reporting a diverse incidence and poor overall outcomes using varied non-contemporaneous treatment protocols adapted from the developed world. A comprehensive countrywide approach to diagnosis, treatment, and follow-up and the potential incorporation of novel therapies could improve the prognosis and outcomes of adult ALL in India.

13.
JCO Glob Oncol ; 6: 1684-1695, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33156719

RESUMO

PURPOSE: Infections remain a major challenge in the treatment of acute myeloid leukemia (AML). Induction-related mortality reported in the literature is approximately < 5% in clinical trials. However, the real-world scenario is different, especially in developing countries, given the high incidence of multidrug-resistant (MDR) organisms, high incidence of fungal pneumonia at baseline, and significant delay before initiation of chemotherapy. We aimed to look at contemporary infections and infection-related mortality and analyze the patterns of infections. MATERIALS AND METHODS: This retrospective study was conducted at a large tertiary care oncology center in India. Patients with newly diagnosed AML who were older than age 15 years, considered fit for intensive therapy, and treated in the general wards of the adult hematolymphoid unit from March 1, 2014, until December 31, 2015, were included. RESULTS: One hundred twenty-one patients were treated during the study period. The most common presenting complaint was fever (85%). The focus of infection at presentation was found in 63% of patients, with respiratory infection being the most common (47%). MDR organisms were isolated in 55% of patients during induction from various foci. Klebsiella pneumoniae was the most common blood culture isolate (42.9%). Fungal pneumonia was diagnosed in 55% of patients during induction despite antifungal prophylaxis. Treatment-related mortality was 10.7% in all phases, with an induction mortality rate of 7.4%. Complete remission was attained in 69% of patients. Of all patients who received induction chemotherapy, 74% completed all three consolidation cycles. The 121 patients were followed up for a median period of 53 months. Four-year event-free survival was 35.8%, and 4-year overall survival was 41.5%. CONCLUSION: Infections and infection-related mortality are major challenges during AML induction. Gram-negative MDR and fungal infections are particularly common in our region.

14.
Cancer Med ; 9(23): 8747-8753, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33128509

RESUMO

BACKGROUND: There is limited data on outcomes in cancer patients with coronavirus disease 2019 (COVID-19) from lower middle-income countries (LMICs). PATIENTS AND METHODS: This was an observational study, conducted between 12 April and 10 June 2020 at Tata Memorial centre, Mumbai, in cancer patients undergoing systemic therapy with laboratory confirmed COVID-19. The objectives were to evaluate cumulative 30-day all-cause mortality, COVID-19 attributable mortality, factors predicting mortality, and time to viral negativity after initial diagnosis. RESULTS: Of the 24 660 footfalls and 7043 patients evaluated, 230 patients on active systemic therapy with a median age of 42 (1-75) years were included. COVID-19 infection severity, as per WHO criteria, was mild, moderate, and severe in 195 (85%), 11 (5%), and 24 (11%) patients, respectively. Twenty-three patients (10%) expired during follow-up, with COVID-19 attributable mortality seen in 15 patients (6.5%). There were no mortalities in the pediatric cohort of 31 (14%) patients. Advanced stage cancer being treated with palliative intent vs others [30-day mortality 24%% vs 5%, odds ratio (OR) 5.6, 95% CI 2.28-13.78, P < .001], uncontrolled cancer status vs controlled cancer (30-day mortality37.5%% vs 4%%, OR 14, 95% CI 4.46-44.16, P < .001) and severe COVID-19 vs mild COVID-19 (30-day mortality 71% vs 3%, OR 92.29, 95% CI 26.43-322.21, P < .001) were significantly associated with mortality. The median time to SARS-CoV-2 RT-PCR negativity was 17 days [interquartile range (IQR)17-28) in the cohort. CONCLUSIONS: The mortality rates in cancer patients with COVID-19 who are receiving systemic anti-cancer therapy in LMICSs are marginally higher than that reported in unselected COVID-19 cohorts with prolonged time to viral negativity in a substantial number of patients. The pediatric cancer patients tended to have favorable outcomes.


Assuntos
Antivirais/uso terapêutico , COVID-19/prevenção & controle , Neoplasias/terapia , SARS-CoV-2/efeitos dos fármacos , Adolescente , Adulto , Idoso , COVID-19/epidemiologia , COVID-19/virologia , Criança , Pré-Escolar , Comorbidade , Feminino , Humanos , Índia/epidemiologia , Lactente , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Pandemias , Estudos Prospectivos , SARS-CoV-2/fisiologia , Taxa de Sobrevida , Adulto Jovem
15.
Artigo em Inglês | MEDLINE | ID: mdl-33090916

RESUMO

Purpose: There is lack of consensus on management of adolescent and young adult (AYA) Hodgkin lymphoma with respect to chemotherapy approach (adult or pediatric). Hence we sought to evaluate the efficacy and safety of Adriamycin, Bleomycin, Vinblastine and Dacarbazine (ABVD) chemotherapy in AYA Hodgkin lymphoma. Patients and Methods: It is a retrospective, observational, single-center study. From January 2013 to December 2016, all consecutive patients with AYA (15-25 years, all stages) were analyzed. The primary endpoint of the study was event-free survival (EFS). Secondary endpoints were complete response rates (CR) and overall survival (OS). Results: A total of 220 patients (70% men) with median age 20 years were evaluated. A significant proportion of patients had adverse features such as stage III/IV disease (63%), bulky disease (63%), extranodal involvement (37%), and marrow involvement (22%). After two cycles and end of therapy, 77% patients achieved complete response. Primary progressive disease was seen in 6% patients. With a median follow-up of 2.6 years, 19 (8.6%) patients relapsed, 1 patient developed second malignancy, and 6 patients died. Three-year EFS and OS were 81.3% and 97%, respectively. Bleomycin-induced lung injury was seen in 16% patients. On multivariate analysis stage at presentation, bone marrow involvement, partial response at interim positron emission tomography and International prognosis score (IPS) >3 were predictors of poor EFS. Conclusion: ABVD is an effective and safe regimen in AYA Hodgkin lymphoma. Advanced disease with high IPS (>3) score needs an early escalation approach to escBEACOPP regimen.

16.
Hematol Oncol ; 38(5): 808-816, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32893896

RESUMO

The high expression of brain and acute leukemia, cytoplasmic (BAALC) and ETS-related gene (ERG) has been reported to influence the outcome in acute myeloid leukemia (AML), but due to limited prospective studies, their role as prognostic factors is unclear. At diagnosis, the prognostic value of BAALC and ERG expression with respect to other cytogenetic and molecular markers was analyzed in 149 AML patients. Patients were divided into quartiles which resulted in the formation of four groups (G1-G4) based on expression values of BAALC and ERG and clinical response defined across groups. Groups with similar survival probabilities were merged together and categorized subsequently as high versus low expressers. Patients with high BAALC and ERG expression had significantly lower overall survival (OS; BAALC: p = 0.001 at 5 years 29.4% vs. 69.8%; ERG: p < 0.0001 at 5 years 4% vs. 50.4%) and disease-free survival (BAALC: p = 0.001 at 5 years 19.5% vs. 69.8%; ERG: p < 0.0001 at 5 years 4.2% vs. 47%). Patients were further stratified combining BAALC and ERG expression in an integrative prognostic risk score (IPRS). After a median follow-up of 54 months (95% CI 45-63 months) among survivors, IPRS for high versus low expressers was a significant predictor for OS (BAALC + ERG: 4% vs. 71.6%, p < 0.0001) and DFS (BAALC + ERG: 4.5% vs. 74.1%, p < 0.0001). In a multivariate model, IPRS of BAALC + ERG expression retained prognostic significance for OS (hazard ratio [HR] 2.96, 95%CI 1.91-4.59, p < 0.001) and DFS (HR 3.61, 95%CI 2.26-5.76, p < 0.001).


Assuntos
Biomarcadores Tumorais , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Proteínas de Neoplasias/genética , Adolescente , Adulto , Aberrações Cromossômicas , Análise Mutacional de DNA , Feminino , Regulação da Expressão Gênica , Humanos , Cariotipagem , Leucemia Mieloide Aguda/diagnóstico , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Medição de Risco , Análise de Sobrevida , Regulador Transcricional ERG/genética , Adulto Jovem
17.
Int J Hematol ; 112(6): 835-840, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32876851

RESUMO

Hematopoietic stem and progenitor cell (HSPC) mobilization regimens in multiple myeloma typically use filgrastim (GCSF) alone or combination of GCSF with plerixafor or high-dose cyclophosphamide. Murine model and human studies have shown HSPC mobilization potential of bortezomib. A total of 37 patients underwent mobilization using bortezomib 1.3 mg/m2 on day 1, 4, 8 and 11, cyclophosphamide 1 g/m2 on day 8 and 9, and GCSF 10 µg/kg from day 10 (B-Cy-GCSF). This regimen was compared with our earlier cohort of patients where cyclophosphamide was given at dose of 1 g/m2 on day 1 and day 2 followed by GCSF 10 µg/kg from day 4 (Cy-GCSF). In B-Cy-GCSF group, median CD34 cells collected were 9.21 × 106/kg (range 4.95-17.1) while in the Cy-GCSF cohort, the median CD34 cell yield was 8.2 × 106/kg (0.4-24.2). Target CD34 cells yield of 5 × 106/kg was achieved with single apheresis in 58.6% of patients after B-Cy-GCSF mobilization as compared to 44.3% in Cy-GCSF group (p = 0.07). Three patients failed mobilization after Cy-GCSF, while no patients failed mobilization in bortezomib group. Addition of bortezomib to Cy-GCSF mobilization showed a trend towards increased CD34 collection and reduced need for apheresis sessions.


Assuntos
Bortezomib/administração & dosagem , Ciclofosfamida/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/terapia , Adulto , Idoso , Antígenos CD34/metabolismo , Remoção de Componentes Sanguíneos , Feminino , Filgrastim/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade
18.
Leuk Lymphoma ; 61(13): 3154-3160, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32757686

RESUMO

Panel based next generation sequencing was performed on a discovery cohort of AML with RUNX1-RUNX1T1. Supervised machine learning identified NRAS mutation and absence of mutations in ASXL2, RAD21, KIT and FLT3 genes as well as a low mutation to be associated with favorable outcome. Based on this data patients were classified into favorable and poor genetic risk classes. Patients classified as poor genetic risk had a significantly lower overall survival (OS) and relapse free survival (RFS). We could validate these findings independently on a validation cohort (n = 61). Patients in the poor genetic risk group were more likely to harbor measurable residual disease. Poor genetic risk emerged as an independent risk factor predictive of inferior outcome. Using an unbiased computational approach based we provide evidence for gene panel-based testing in AML with RUNX1-RUNX1T1 and a framework for integration of genomic markers toward clinical decision making in this heterogeneous disease entity.


Assuntos
Subunidade alfa 2 de Fator de Ligação ao Core , Leucemia Mieloide Aguda , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Genômica , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Aprendizado de Máquina , Mutação , Proteína 1 Parceira de Translocação de RUNX1/genética
19.
Cancer Rep (Hoboken) ; 3(5): e1264, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32761885

RESUMO

BACKGROUND: Primary lymphomas involving the female genital tract are rare, and those arising from cervix are extremely uncommon. They are often misdiagnosed because of their rarity. METHODS AND CASES: The treatment and clinical outcomes of the four cases treated at our institution were compared with the previously published studies. Written informed consent was taken. We highlight four cases of primary diffuse large B-cell lymphoma of cervix treated at our institution with immunochemotherapy and radiotherapy. The mean age was 50 years (range, 39-62 years). Three patients had stage I disease while one had stage II disease. All the patients were in complete remission following treatment with immunochemotherapy and radiation therapy. The average disease free survival was 20 months (range, 8-43 months). None of the patients had any local or systemic relapse. CONCLUSION: These cases highlight the physicians to be aware of this entity as their management, natural history and prognosis is completely different from squamous carcinomas of the cervix. Surgery should not be attempted in these patients. Immunochemotherapy and radiotherapy results in favorable clinical outcomes.

20.
Blood Cells Mol Dis ; 85: 102465, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32693366

RESUMO

Ploidy, besides known translocations in lymphoblasts, is a strong predictor of prognosis in B- cell progenitor acute lymphoblastic leukemia (BCP-ALL). While hyperdiploidy with >50 chromosomes shows a favourable outcome, hypodiploidy with <45 chromosomes have a dismal clinical outcome. However, there exists a small subset where both the hypodiploid and hyperdiploid clones are apparent either by cytogenetics or flow cytometry and are defined partially masked hypodiploids or mosaics based on the percentage of clonal population. These patients are essentially hypodiploids, and show the hyperdiploid clone as a consequence of endoreduplication of the primary hypodiploid clone- A phenomenon of successive replication of genome without mitosis (cytokinesis) resulting in increased ploidy. In the current study, we present the complete clinical, hematological and cytogenetic profile of 11 such newly diagnosed mosaics or partially masked hypodiploid BCP-ALL cases.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Adolescente , Adulto , Criança , Pré-Escolar , Análise Citogenética , Endorreduplicação , Feminino , Humanos , Masculino , Ploidias , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Prognóstico , Translocação Genética , Adulto Jovem
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