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Globally, overall survival (OS) of older patients with AML continues to be suboptimal with very little data from India. In a multicenter registry analysis, we evaluated 712 patients with AML older than 55 years. Only 323 (45.3%) underwent further treatment, of which 239 (74%) received HMAs, and 60 (18%) received intensive chemotherapy (IC). CR was documented in 39% of those receiving IC and 42% after HMAs. Overall, 100 (31%) patients died within 60 days of diagnosis, most commonly due to progressive disease (47%) or infections (30%). After a median follow-up of 176 days, 228 (76%) of patients had discontinued treatment. At one year from diagnosis, 211 (65%) patients had died, and the median OS was 186 days (IQR, 137-234). Only 12 (3.7%) patients underwent stem cell transplantation. Survival was significantly lower for those older than 60 years (p < 0.001). Patients who died had a higher median age (p = .027) and baseline WBC counts (p = .006). Our data highlights suboptimal outcomes in older AML patients, which are evident from 55 years of age onwards, making it necessary to evaluate HMA and targeted agent combinations along with novel consolidation strategies to improve survival in this high-risk population.
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BACKGROUND: Vaccine-induced thrombotic thrombocytopenia (VITT) is a rare but devastating adverse event following adenoviral vector-based vaccinations for COVID-19, resulting in thrombosis, especially of the cerebral and splanchnic vasculature. Despite the progress in laboratory techniques for early diagnosis, VITT remains a clinical diagnosis supplemented by coagulation studies. We report on VITT for the first time from India. CASE: We describe cortical venous sinus thrombosis and intracerebral bleed associated with severe thrombocytopenia in two young men who had no other contributory cause besides a recent ChAdOx1 nCoV-19 vaccination. The diagnosis was supported with PF-4 antibodies in one patient. The second patient's test could not be processed to technical limitations. Both patients were treated with IVIG at 1 g/kg for 2 days and anticoagulation (Apixaban). One patient fully recovered with no residual deficits, and the other is under treatment and recovering. CONCLUSION: VITT can cause devastating fatality and morbidity in otherwise healthy patients via potential immune-mediated effects. Clinicians should have a high suspicion index and treat VITT in the appropriate setting even if the PF-4 antibody testing by ELISA is unavailable or delayed. Though counterintuitive, clinicians must not delay the administration of non-heparin anticoagulation, IVIG and restrict platelet transfusion even in the presence of intracerebral haemorrhage.
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BACKGROUND: Multisystem Inflammatory Syndrome in Neonates (MIS-N) can occur following antenatal COVID- 19 infection in the mother. Here we report a rare case of a neonate with Hemophilia A and MIS-N. CASE PRESENTATION: A 2-day-old baby presented with an intramuscular hematoma, neonatal seizures, and isolated activated partial thromboplastin time (APTT) prolongation. The neurosonogram showed a subdural hematoma. A diagnosis of Hemophilia A was made and was confirmed by factor 8 assay and genetic analysis. Supportive measures and Factor 8 replacement was initiated. A rising trend of inflammatory markers and an ongoing need for mechanical ventilation were noted. As there was a history of COVID-19 in the mother in the third trimester, MIS-N was diagnosed. The baby was treated with intravenous immunoglobulin (IVIG) and steroids, and there was an improvement in the clinical and laboratory markers. However, the baby developed seizures on day 16. There was an increase in the subdural hemorrhage and a further rise in inflammatory markers. A craniostomy and hematoma evacuation was done and the baby improved. CONCLUSION: The concurrent occurrence of hemophilia A with intracranial bleed, and MIS-N in a neonate is a diagnostic challenge. It is important to have a high index of suspicion to ensure timely diagnosis and treatment of MIS-N in this pandemic era.
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COVID-19 , Hemofilia A , Factor VIII , Femenino , Hematoma/complicaciones , Hematoma/etiología , Hematoma Subdural/diagnóstico , Hematoma Subdural/etiología , Hemofilia A/complicaciones , Hemofilia A/diagnóstico , Humanos , Recién Nacido , Embarazo , Convulsiones/complicaciones , Síndrome de Respuesta Inflamatoria Sistémica/complicaciones , Síndrome de Respuesta Inflamatoria Sistémica/diagnósticoRESUMEN
Hemophilia A is an inherited bleeding disorder, seen in 1 in 10,000 live births. It is characterized by an increased risk of bleeding, especially involving the musculoskeletal system. Central nervous system bleeding, including brain and spinal cord bleed is rare in the absence of overt trauma, seen in <5% patients. Epidural spinal bleeding in hemophilia is even rarer, and described in <20 patients so far in literature. We describe a young boy who presented with a cervical spine epidural bleed, and was managed conservatively without any sequelae. We also look at the controversies and recent evidence weighing surgical and conservative management of such bleeds.
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Hematoma Espinal Epidural/etiología , Hemofilia A/complicaciones , Niño , Manejo de la Enfermedad , Hematoma Espinal Epidural/dietoterapia , Hemorragia/etiología , Humanos , Masculino , Columna Vertebral/patología , Resultado del TratamientoRESUMEN
Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a distinct subtype of peripheral T-cell lymphoma associated with aggressive clinical behavior. Since its original description, it has continued to be a rare disease, and <200 cases have been reported in literature. We report an 11-year-old boy who presented with SPTCL and hemophagocytic lymphohistiocytosis (HLH) and responded to high-dose multiagent chemotherapy. He presented with steroid refractory erythematous, raised plaques over his face, trunk, and limbs over a period of 15 months treated elsewhere. Repeat evaluation in our center was consistent with SPTCL with features of HLH. He was initiated on therapy with the BFM90 protocol, which led to complete morphologic and biochemical remission. No single-best treatment regimen has been described for SPTCL with HLH in literature, and high-dose chemotherapy has shown good long-term remissions in the literature. The presence of SPTCL with HLH and systemic symptoms should prompt treatment with high-dose multiagent chemotherapy rather than Cyclophosphamide, Vincristine, Adriamycin, Prednisolone-like therapy. BFM90 is one such regimen that is well tolerated, and it can induce significant clinical and biochemical responses.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfohistiocitosis Hemofagocítica/tratamiento farmacológico , Linfoma de Células T/tratamiento farmacológico , Paniculitis/tratamiento farmacológico , Niño , Ciclofosfamida/administración & dosificación , Humanos , Linfohistiocitosis Hemofagocítica/complicaciones , Linfohistiocitosis Hemofagocítica/patología , Linfoma de Células T/complicaciones , Linfoma de Células T/patología , Masculino , Paniculitis/complicaciones , Paniculitis/patología , Prednisolona/administración & dosificación , Pronóstico , Vincristina/administración & dosificaciónRESUMEN
Hematopoietic stem cell transplantation (HSCT) remains the only curative treatment in patients with ß-thalassemia major. A matched sibling or a related donor is usually found in only 25%-30% of the patients. There are limited data on matched unrelated donor (MUD) transplants from India. We reviewed HSCT outcome in 56 children with TM who underwent 57 transplants at our center. Related donor (RD) (n=43) and MUD (n=14) transplants were performed with TreoFluT-based conditioning regimen in majority (95%) of patients. Peripheral blood stem cells (PBSC) were the preferred (85%) source of stem cells. The overall survival (OS) at 1 year in RD and MUD groups was 87.6±5.2% and 85.7±9.4% at a median follow-up of 25 (1-92) months and 22.5 (1-50) months, respectively (P=.757). The thalassemia-free survival (TFS) at 1 year was 87.6±5.2% and 77.1±11.7% with a median follow-up of 24 (1-92) and 16.5 (1-50) months, respectively (P=.487). Although acute (14% vs 64%) and chronic graft-versus-host disease (GVHD) (13.9% vs 42.9%), infectious (39.5% vs 71.4%), and non-infectious (37.2% vs 78.5%) complications are higher in MUD transplant group, the present data show a comparable OS and TFS among RD and MUD group with treosulfan-based regimen using PBSC grafts.
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Trasplante de Células Madre Hematopoyéticas/métodos , Donante no Emparentado , Talasemia beta/terapia , Adolescente , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , India , Lactante , Masculino , Estudios Retrospectivos , Resultado del TratamientoAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Hematología/estadística & datos numéricos , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/economía , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bases de Datos Factuales , Progresión de la Enfermedad , Estudios de Seguimiento , Hematología/normas , Humanos , India/epidemiología , Infecciones/epidemiología , Infecciones/mortalidad , Cumplimiento de la Medicación/psicología , Cumplimiento de la Medicación/estadística & datos numéricos , Neoplasia Residual/epidemiología , Evaluación de Resultado en la Atención de Salud , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Estudios Retrospectivos , Factores Socioeconómicos , Análisis de Supervivencia , Adulto JovenRESUMEN
The management of acute myeloid leukaemia (AML) in India remains a challenge. In a two-year prospective study at our centre there were 380 newly diagnosed AML (excluding acute promyelocytic leukaemia, AML-M3) patients. The median age of newly diagnosed patients was 40 years (range: 1-79; 12.3% were ≤ 15 years, 16.3% were ≥ 60 years old) and there were 244 (64.2%) males. The median duration of symptoms prior to first presentation at our hospital was 4 weeks (range: 1-52). The median distance from home to hospital was 580 km (range: 6-3200 km). 109 (29%) opted for standard of care and were admitted for induction chemotherapy. Of the 271 that did not take treatment the major reason was lack of financial resources in 219 (81%). There were 27 (24.7%) inductions deaths and of these, 12 (44.5%) were due to multidrug-resistant gram-negative bacilli and 12 (44.5%) showed evidence of a fungal infection. The overall survival at 1 year was 70.4% ± 10.7%, 55.6% ± 6.8% and 42.4% ± 15.6% in patients aged ≤ 15 years, 15 - 60 years and ≥ 60 years, respectively. In conclusion, the biggest constraint is the cost of treatment and the absence of a health security net to treat all patients with this diagnosis.
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Leucemia Mieloide Aguda/epidemiología , Leucemia Mieloide Aguda/terapia , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Humanos , India/epidemiología , Lactante , Leucemia Mieloide Aguda/economía , Leucemia Mieloide Aguda/mortalidad , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Adulto JovenRESUMEN
Background and aims The second wave of coronavirus disease 2019 (COVID-19) has been devastating in India and many developing countries. The mortality reported has been 40% higher than in the first wave, overwhelming the nation's health infrastructure. Despite a better understanding of the disease and established treatment protocols including steroids and heparin, the second wave was disastrous. Subsequent waves have the potential to further cripple healthcare deliveries, also affecting non-COVID-19 care across many developing economies. It is then important to identify and triage high-risk patients to best use the limited resources. Routine tests such as neutrophil and monocyte counts have been identified but have not been successfully validated uniformly, and their utility is still being understood in COVID-19. Various predictive models that are available require online resources and calculators and additionally await validation across all populations. These, although useful, might not be available or accessible across all institutions. It is then important to identify easy-to-use scores that utilize tests done routinely. In identifying with this goal, we did a retrospective review of the institutional database to identify potential predictors of intensive care unit (ICU) admission and mortality in patients hospitalized during the second wave who accessed healthcare at our academic setup. Results Three predictors of mortality and four predictors of ICU admission were identified. Absolute neutrophil count was a common predictor of both ICU admission and mortality but with two separate cut points. An absolute neutrophil count of >4,200 predicted need for ICU admission (odds ratio (OR): 3.1 (95% confidence interval (CI): 2.0, 4.8)), and >7,200 predicted mortality (adjusted OR: 4.2 (95% CI: 1.9, 9.4)). We observed that a blood urea level greater than 45 was predictive of needing ICU care (adjusted OR: 8.0 (95% CI: 3.7, 17.6)). In our dataset, serum ferritin of >500 was predictive of ICU admission (adjusted OR: 2.7 (95% CI: 1.2, 5.9)). We noted a right shift of partial pressure (p50 is the oxygen tension at which hemoglobin is 50% saturated) (p50c) in SARS-CoV-2 as a predictor of ICU care (OR: 2.6 (95% CI: 1.7, 3.9)) when partial pressure is >26.5. In our analysis, a serum protein of less than 7 g/dL (OR: 2.8 (95% CI: 1.7, 4.4)) was a predictive variable for ICU admission. An LDH value of >675 was predictive of severity with a need for ICU admission (OR: 9.2 (95% CI: 5.4, 15.5)) in our series. We then assigned a score to each of the predictive variables based on the adjusted odds ratio. Conclusion We identified a set of easy-to-use predictive variables and scores to recognize the subset of patients hospitalized with COVID-19 with the highest risk of death or clinical worsening requiring ICU care.
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BACKGROUND: Allogeneic stem cell transplant is the only curative treatment for Wiskott-Aldrich syndrome. CASE CHARACTERISTICS: 18-months-old boy with no sibling, cord blood or matched unrelated donor transplant options. OUTCOME: Doing well 7 years after haplo-identical stem cell transplantation using unmanipulated bone marrow as the stem cell source. MESSAGE: Father as a haplo-identical donor is a feasible option.
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Trasplante de Células Madre/métodos , Síndrome de Wiskott-Aldrich/cirugía , Humanos , Lactante , MasculinoRESUMEN
BACKGROUND: Variation in terms of outcome and toxic side effects of treatment exists among acute myeloid leukemia (AML) patients on chemotherapy with cytarabine (Ara-C) and daunorubicin (Dnr). Candidate Ara-C metabolizing gene expression in primary AML cells is proposed to account for this variation. METHODS: Ex vivo Ara-C sensitivity was determined in primary AML samples using MTT assay. mRNA expression of candidate Ara-C metabolizing genes were evaluated by RQPCR analysis. Global gene expression profiling was carried out for identifying differentially expressed genes between exvivo Ara-C sensitive and resistant samples. RESULTS: Wide interindividual variations in ex vivo Ara-C cytotoxicity were observed among samples from patients with AML and were stratified into sensitive, intermediately sensitive and resistant, based on IC50 values obtained by MTT assay. RNA expression of deoxycytidine kinase (DCK), human equilibrative nucleoside transporter-1 (ENT1) and ribonucleotide reductase M1 (RRM1) were significantly higher and cytidine deaminase (CDA) was significantly lower in ex vivo Ara-C sensitive samples. Higher DCK and RRM1 expression in AML patient's blast correlated with better DFS. Ara-C resistance index (RI), a mathematically derived quotient was proposed based on candidate gene expression pattern. Ara-C ex vivo sensitive samples were found to have significantly lower RI compared with resistant as well as samples from patients presenting with relapse. Patients with low RI supposedly highly sensitive to Ara-C were found to have higher incidence of induction death (p = 0.002; RR: 4.35 [95% CI: 1.69-11.22]). Global gene expression profiling undertaken to find out additional contributors of Ara-C resistance identified many apoptosis as well as metabolic pathway genes to be differentially expressed between Ara-C resistant and sensitive samples. CONCLUSION: This study highlights the importance of evaluating expression of candidate Ara-C metabolizing genes in predicting ex vivo drug response as well as treatment outcome. RI could be a predictor of ex vivo Ara-C response irrespective of cytogenetic and molecular risk groups and a potential biomarker for AML treatment outcome and toxicity. Original submitted 22 December 2014; Revision submitted 9 April 2015.