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1.
Cancer Med ; 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34786866

RESUMO

BACKGROUND: There is paucity of data regarding clinical characteristics, laboratory parameters and outcomes of coronavirus disease (COVID-19) in cancer versus non-cancer patients, particularly from India. MATERIALS AND METHODS: This was an observational, single-centre, retrospective analysis of patients with laboratory-confirmed COVID-19 hospitalised in our institution between 22 May 2020 and 1 December 2020. We compared baseline clinical characteristics, laboratory parameters and outcomes of COVID-19 (overall mortality, time to discharge) between cancer and non-cancer patients. RESULTS: A total of 200 COVID-19 infection episodes were analysed of which 109 (54.5%) were patients with cancer and 91 (45.5%) were patients without cancer. The median age was 43 (interquartile range [IQR]:32-57), 51 (IQR: 33-62) and 38 (IQR: 31.5-49.3) years; of whole cohort, cancer and non-cancer patients, respectively. Comparison of outcomes showed that oxygen requirement (31.2% [95% CI: 22.6-40.7] vs. 17.6% [95% CI: 10.4-26.9]; p = 0.03), median time to discharge (11 days [IQR: 6.75-16] vs. 6 days [IQR: 3-9.75]; p < 0.001) and mortality (10.0% [95% CI: 5.2-17.3] vs. 1.1% [95% CI: 0.03-5.9]; p = 0.017) were significantly higher in patients with cancer. In univariable analysis, factors associated with higher mortality in the whole cohort included diagnosis of cancer (10.1% vs. 1.1%; p = 0.027; odds ratio [OR]: 7.04), age ≥60 (17.4% vs. 2.6%; p = 0.001; OR: 7.38), oxygen requirement (22% vs. 0.6%; p < 0.001; OR: 29.01), chest infiltrates (19.2% vs. 1.4%; p < 0.001; OR: 22.65), baseline absolute lymphocyte count <1 × 109 /L (10.8% vs. 1.9%; p = 0.023; OR:5.1), C-reactive protein >1 mg% (12.8% vs. 0%; p = 0.027; OR: 24.69), serum procalcitonin >0.05 ng/ml (22.65% vs. 0%; p = 0.004; OR: 4.49) and interleukin-6 >6 pg/ml (10.8% vs. 1.3%; p = 0.036; OR: 3.08). In multivariable logistic regression, factors significantly associated with mortality were oxygen requirement (p = 0.005; OR: 13.11) and high baseline procalcitonin level (p = 0.014; OR: 37.6). CONCLUSION: Cancer patients with COVID-19 have higher mortality and require longer hospital stay. High procalcitonin levels and oxygen requirement during admission are other factors that affect outcomes adversely.

2.
Am J Blood Res ; 11(5): 528-533, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34824885

RESUMO

The prognosis of patients with relapsed Early Thymic Precursor acute lymphoblastic leukemia (ETP-ALL) remains poor. Unlike B cell Precursor-ALL (BCP-ALL), there are no approved targeted therapies for ETP-ALL. Recent studies have identified a consistent expression of CD38 on the blasts of patients with T-ALL (both ETP-ALL and non ETP-ALL). Pre-clinical studies indicate that CD38 expression persists on the blasts of T-ALL even after receipt of conventional chemotherapy. These findings make CD38 an attractive targetable surface protein for patients with relapsed refractory T-ALL. We were the first to describe the clinical use of daratumumab in a patient of ETP-ALL, with relapsed disease post allogeneic transplant. We describe here the long term outcome of this patient more than 3 years after starting single agent daratumumab.

3.
Am J Blood Res ; 11(5): 564-570, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34824888

RESUMO

OBJECTIVES: Lenalidomide is an active agent in acute myeloid leukemia (AML); response rates are about 15-30%. There are no well-defined predictive factors for benefit from lenalidomide in AML. One of the mechanisms of lenalidomide is natural killer (NK) cell activation; hence human leukocyte antigen (HLA) class I alleles (serving as killer immunoglobulin-like receptor ligands) could play a predictive role. We here evaluate the same when lenalidomide was used as a bridge to transplant. METHODS: Consecutive AML patients started on lenalidomide as bridge to transplant between Aug-2013 to Aug-2018 were included in this single centre retrospective analysis. The starting dose and schedule of lenalidomide were at the discretion of the treating clinician. Lenalidomide was scheduled to be stopped about 2-4 weeks prior to planned transplant admission (or was stopped earlier if there was intolerance). For this study, event was defined as progression/relapse while on lenalidomide or within 4 weeks of stopping the drug. The primary endpoint was event free survival (EFS). Those who underwent transplant without an event were censored on the day of transplant. Toxicities and post-transplant outcomes were secondary endpoints. RESULTS: Twelve patients (8 males, median age 29 years) were included. At start of lenalidomide, 7 had complete remission (CR)-1 (measurable residual disease or MRD by flow cytometry was positive in 3, negative in 3, and 1 unknown), 4 CR-2 (all MRD negative) and 1 active disease. In the whole cohort, median EFS was not reached with projected 3 year EFS being 80%. There was a significantly reduced risk of event with HLA A*24 (0% vs 75%, P=0.018) or with HLA B*40 (0% vs 60%, P=0.045). Only 1 patient needed discontinuation due to toxicities (cytopenias). Among patients who underwent transplant, grade II-IV acute graft versus host disease (GVHD) was seen in 83%. CONCLUSIONS: This is first study to show that HLA alleles may have a bearing on the effect of lenalidomide in AML and could serve as predictive biomarkers. These findings need to be confirmed in larger prospective studies.

4.
Psychooncology ; 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34435720

RESUMO

OBJECTIVE: Families of children with cancer undergoing treatment during COVID-19 pandemic represent a vulnerable population for psychological distress and early identification and remedial measures are imperative for wellbeing of both the children and the caregivers. This article reports the results of assessment of psychological distress in primary caregivers of children with cancer undergoing treatment at a tertiary care center. METHODS: Primary caregivers of children with cancer (≤15 years) taking treatment at our institute during the period of July 2020 to August 2020 were prospectively evaluated for psychological distress using Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) tools over a telephonic call. There were 2 cohorts, A and B (50 participants each) depending on whether child was diagnosed with COVID-19 or not respectively during the study period. RESULTS: The assessment tool, PHQ-9 showed a score of ≥10 in 13% (n = 13) participants (95%CI:7.1%-21.2%) in the entire cohort and in 16% (n = 8, 95%CI:5.8%-26.2%) and 10% (n = 5, 95%CI:1.7%-18.3%) participants in cohort A and cohort B respectively. GAD-7 showed a score of ≥8 in 18% (n = 18) participants (95%CI:11.0%-27.0%) in the entire cohort and in 20% (n = 10, 95%CI:8.9%-31.1%) and 16% (n = 8, 95%CI:5.8%-26.2%) participants in cohort A and cohort B respectively. All participants were assessed, and supportive psychotherapeutic interventions administered over telephonic call. CONCLUSIONS: Primary caregivers should be assessed and followed up for psychological distress irrespective of other co-existing factors. Robust support systems built over time could help withstand the exceptional strain of a major surge during a pandemic.

5.
Indian J Pediatr ; 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34378149

RESUMO

OBJECTIVE: To report the experience with COVID-19 in children with cancer at the largest tertiary-cancer care and referral center in India. METHODS: This study is a single tertiary center experience on COVID-19 in children with cancer and continuation of cancer-directed therapy in them. Children ≤ 15 y on active cancer treatment detected with COVID-19 until September 15th, 2020 were prospectively followed up in the study. Patients were managed in accordance with well-laid guidelines. Treatment was continued for children with COVID-19 who were clinically stable and on intensive treatment for various childhood cancers. RESULTS: One hundred twenty-two children (median age 8 y; range 1-15 y, male:female 1.7:1) with cancer were diagnosed with COVID-19. Of 118 children, 99 (83.9%), 60 (50.8%), 43 (36.4%), 26 (22.0%), and 6 (5.1%) had RT-PCR positivity at 14, 21, 28, 35, and 60 d from diagnosis of COVID-19, respectively. Scheduled risk-directed intravenous chemotherapy was delivered in 70 (90.9%) of 77 children on active systemic treatment with a median delay of 14 d (range 0-48 d) and no increased toxicities. All-cause mortality rate was 7.4% (n = 9) and COVID-19 related mortality rate was 4.9% (n = 6). One hundred-fifteen (94.2%) children with COVID-19 did not require any form of respiratory support during the course of infection. CONCLUSIONS: COVID-19 was not a major deterrent for the continuation of active cancer treatment despite persistent RT-PCR positivity. The long-term assessment of treatment adaptations requires further prospective follow-up and real-time addressal.

7.
Transpl Infect Dis ; 23(4): e13576, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33523551

RESUMO

Recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT) are an immunocompromised group who are likely to develop severe complications and mortality because of coronavirus disease 2019 (COVID-19). We report here a 61-year-old male patient of primary myelofibrosis who underwent an allo-HSCT 6 years earlier, had chronic graft-versus-host disease (cGVHD) involving the liver, lung, eyes, and skin, (with recurrent episodes of pulmonary infections) who developed severe COVID-19. The patient was treated with tocilizumab, and a combination of lopinavir/ritonavir, ribavirin, interferon-ß1b. He was discharged after 31 days with full recovery. Tocilizumab, a humanized monoclonal antibody against IL6, has been shown to benefit respiratory manifestations in severe COVID19. However, this is first report, to our knowledge, of its use and benefit in a post HSCT recipient.


Assuntos
COVID-19 , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Anticorpos Monoclonais Humanizados , Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2 , Transplante de Células-Tronco/efeitos adversos
8.
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
9.
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
11.
Front Immunol ; 10: 490, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30949167

RESUMO

Fanconi anemia (FA) is a rare inherited syndrome characterized by progressive bone marrow failure (BMF), abnormal skin pigmentation, short stature, and increased cancer risk. BMF in FA is multifactorial and largely results from the death of hematopoietic stem cells due to genomic instability. Also, inflammatory pathology in FA has been previously reported, however the mechanism is still not clear. In literature, decreased NK-cell count and/or impaired NK-cell activity, along with other immunological abnormalities have been described in FA-patients (1). However, to the best of our knowledge, this is the first report showing a defective degranulation mechanism leading to abnormal NK-cell cytotoxicity in FA-patients, which may explain the development of a hyperinflammatory response in these patients. This may predispose some patients to develop Hemophagocytic lymphohistiocytosis (HLH) which manifests with prolonged fever, progressive cytopenias and organomegaly. Early diagnosis and initiation of immunosuppressive therapy in these patients will help to better manage these patients. We also propose FA genes to be listed as a cause of familial HLH.


Assuntos
Degranulação Celular/imunologia , Anemia de Fanconi/imunologia , Células Matadoras Naturais/imunologia , Adolescente , Pré-Escolar , Anemia de Fanconi/patologia , Feminino , Humanos , Inflamação/imunologia , Inflamação/patologia , Células Matadoras Naturais/patologia , Masculino
12.
Indian Pediatr ; 51(2): 145-6, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24632697

RESUMO

BACKGROUND: Granulocytic sarcoma, an uncommon solid, extra-medullary tumor is a rare presentation of acute myeloid leukemia. CASE CHARACTERISTICS: A seven-year old boy admitted to the hospital for treatment of leukemia having radiological findings of consolidation in one lung. OBSERVATION/INTERVENTION: A bronchoalveolar lavage was done which was negative for tubercular, bacterial, and fungal infection but showed blast cells. OUTCOME: On day seven of chemotherapy, a repeat chest x-ray showed resolution of the lesion. A high-resolution Computerized tomography of chest repeated after one month of induction showed resolution. MESSAGE: A consolidation on chest radiograph in acute myeloid leukemia can be a granulocytic sarcoma of the lung; a bronchoalveolar lavage may be offered to confirm or refute this diagnosis.


Assuntos
Leucemia Mieloide Aguda/diagnóstico , Neoplasias Pulmonares/diagnóstico , Sarcoma Mieloide/diagnóstico , Antineoplásicos/uso terapêutico , Criança , Diagnóstico Diferencial , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Masculino , Sarcoma Mieloide/tratamento farmacológico
13.
Pediatr Surg Int ; 27(9): 919-23, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21544644

RESUMO

PURPOSE: To analyze the clinical profile, management and outcome of non-hematological tumors in head and neck region in children less than 18 years of age. PATIENTS AND METHODS: Medical records of patients (0-18 years) presenting with non-hematological tumors of head and neck region from 2000 to 2010 were reviewed. RESULT: Out of the 78 patients identified, 50 were males with median age of 14 years (3 months to 18 years). Histologically, 58 out of the 78 patients had malignant tumors and 20 were metastatic at presentation. Common site of tumor origin was noted as thyroid (23/78), salivary glands (21/78) and nasopharynx (13/78). Out of 78 patients, 44 patients were treated by surgery, 26 patients received radiation and 13 patients received chemotherapy, while 9 patients received radio-iodine (I-131) treatment. Median follow up of all cases was 22 months (range 1 month to 8 years). The event free survival was 74.1% and overall survival was 89.6%. Subset analysis revealed patients with thyroid and salivary gland malignancies have excellent survival, while those with squamous cell carcinoma and high risk neuroblastoma had poor outcome. CONCLUSION: This study reveals the interesting profile of head and neck tumors in children, and important role of surgery for favorable outcome.


Assuntos
Neoplasias de Cabeça e Pescoço , Adolescente , Institutos de Câncer , Criança , Pré-Escolar , Feminino , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Lactente , Masculino , Estudos Retrospectivos
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