Long-term real-world outcomes of patients with acute promyelocytic leukaemia treated with arsenic trioxide and all-trans retinoic acid without chemotherapy-a retrospective, single-centre study.

Arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) form the backbone of the treatment of acute promyelocytic leukaemia (APL), with the addition of chemotherapy for high-risk patients. We describe our experience of treating patients with APL of all risk classes with ATO and ATRA without chemotherapeutic agents. Patients received induction with ATO and ATRA followed by three cycles of consolidation with ATO and ATRA (each 1 month apart) after achieving morphological remission. Patients with intermediate- and high-risk disease received a further 2 years of maintenance with ATRA, 6-mercaptopurine and methotrexate. A total of 206 patients were included in the study. The majority of the patients were intermediate risk (51.9%), followed by high risk (43.2%). Differentiation syndrome was seen in 41 patients (19.9%). Overall, 25 patients (12.1%) died within 7 days of initiating therapy. Seven patients relapsed during follow-up. The mean (SD) estimated 5-year event-free survival (EFS) and overall survival (OS) in the entire cohort was 79% [5.8%] and 80% [5.8%] respectively. After excluding patients who died within 7 days of therapy initiation, the mean (SD) estimated 5-year EFS and OS was 90% [5.8%] and 93% [3.9%] respectively. Our study shows that treatment of all risk classes of APL with ATO and ATRA without chemotherapy is associated with excellent long-term outcomes in the real-world setting.

Hematopoietic cell transplantation landscape in India.

Hematopoietic cell transplantation (HCT), commonly known as Bone marrow transplantation (BMT), is a medical procedure used to treat various conditions, including blood cancers, genetic disorders, and certain autoimmune diseases. The procedure involves replacing damaged or diseased bone marrow with healthy stem cells to promote the production of new, healthy blood cells. In India, HCT has been performed for several years in specialized medical centers. India has a growing healthcare infrastructure, and many hospitals are equipped to perform these procedures. Though there are studies on HCTs done at individual transplant centers in India, a comprehensive analysis of the current landscape of HCT in the country is lacking. HCT in India has seen major advances both in the quantity and quality of HCT centers. This review article has attempted to cover the gaps of HCT in India, including its status in the Armed Forces HCT centers.

Successful T replete haploidentical HSCT with post-transplant cyclophosphamide in two patients with Wiskott-Aldrich syndrome.

We describe two young patients with Wiskott-Aldrich Syndrome (WAS) who were treated by T-replete hematopoietic stem cell transplantation (HSCT) from the HLA haploidentical father according to a modified Baltimore protocol. Whereas similar protocols have been successfully used in various malignant and non-malignant diseases, this is the first report for this particular disease. The data being presented pertains to the report about two successful haploidentical transplants with post transplant cyclophosphamide (PTCY) after busulfan-based conditioning.

Diarrheal woes in transplantation from real world settings with special focus on clostridium difficile infection.

Background: Diarrhea is the major cause of discomfort and morbidity of patients undergoing hematopoietic stem cell transplant (HSCT). The cause of diarrhea may be infective or non-infective. Methods: This is a prospective single center observational study from North India conducted over a period of approximately 4 years among 105 patients who underwent HSCT (autologous-72, allogeneic-33). The objective of the study was to identify the overall incidence and characteristics of diarrhea in HSCT in the real world, to evaluate any differences among allogeneic or autologous transplants, incidence of C Difficile among diarrheal patients, and antimicrobial usage among these patients. Results: Diarrhea was present in 89 of 105 patients (84.7%). The mean diarrheal duration was of 8.39±4.57 days (range: 1-24 days). There was non statistical difference between the incidence of diarrhea amongst allogeneic and autologous transplants (78.9% Vs 87.5%). Out of 89 patients with diarrhea, 13 were CDTA positive. We could isolate Clostridium difficile in culture in only 7.6% of patients with CDTA positivity. Metronidazole was the antibiotic of choice for diarrhea in our post-transplant settings. Metronidazole was prescribed for a median duration of 8 days (Range: 3-18 days). Seventeen patients received oral vancomycin with a median duration of 8 days (Range: 5-14 days). Conclusion: We conclude by saying that diarrhea was a common post-transplant morbidity. Clostridium difficile is not common in patients with the diarrhea post hematopoietic stem cell transplant. All cases of diarrhea need not be infective particularly in allogeneic settings.

Prognostic significance of extramedullary disease (EMD) detected on pre-transplant 18F-FDG PET/CT in patients with multiple myeloma: Results of PIPET-M trial.

Background: It is difficult to prognosticate the post-Autologous Stem Cell Transplant (ASCT) responses in multiple myeloma (MM) with the currently available prognostication models. 18F-FDGPET/CT has numerous advantages to prognosticate the post-transplant responses by assessing extramedullary disease (EMD) in addition to the extent of active disease. We aimed at identifying the prognostic value of EMD in predicting progression-free survival (PFS) and overall survival (OS). Methods: This is a single centre prospective study from western India during a study period of 2014-2022 (with a median follow-up of patients of 6 years). All ASCT patients underwent 18F-FDG-PET/CT as part of pre-transplant workup. The conditioning and treatment protocols were not modified based on PET/CT findings. EMD on PET/CT was correlated with pre-transplant biochemical markers and post-ASCT survival/ progression (as defined by revised IMWG criteria). Statistical analysis was done using SPSS ver. 20. Results: Patients with pre-ASCT EMD had a hazard-ratio for post-transplant all-cause mortality of 5.46 (p-0.045). Pre-transplant ß2M and LDH were significantly higher in patients with EMD (p-0.036). The 6-year median OS in patients with and without EMD were 57.1%, and 80.6% respectively. Kaplan-Meier analysis showed poorer OS in patients with EMD χ2 (1-0.496, p-0.481). There was no significant difference in clinical or biochemical EFS among patients with EMD. Conclusion: EMD detected on 18F-FDG-PET/CT has a higher hazard for mortality and is significantly correlated with pre-transplant higher ß2M and LDH levels. Thus, EMD by pre-transplant 18F-FDG-PET/CT has a significant prognostic role.

Bone marrow transplant: A two-decade single centre hematology experience.

Background: Bone Marrow Transplant (BMT) is a curative form of therapy for many hematological disorders in both the adult and pediatric patients. The availability of BMT in the AFMS at AHRR for the last 02 decades has been a game changer for the patients. Methods: We reviewed our BMT data since the inception of the program till Feb 2023. Results: Over 700 patients with more than 23 different types of hematological disorders have undergone this procedure 58%% patients underwent an Autologous BMT and 42% an allogenic BMT. Autologous BMT for Multiple Myeloma and Allogenic BMT for Aplastic Anemia and Acute Leukemias have been the most common indications. 73% patients were adults, and 27% patients were of the pediatric age group. The male: female ratio was 2:1. The spectrum of allogenic Hematopoietic Stem Cell Transplant (HSCT) has expanded from Matched Sibling Donor (MSD) transplants to Matched Unrelated Donor (MUD) Transplants and Haploidentical Donor Transplants. 93% of our Allogenic BMT patients underwent a MSD BMT, 1% MUD BMT and 06% Haploidentical BMT. Today no patient with a malignant hematological disorder requiring a BMT is denied the procedure due to the lack of an HLA donor due to the availability of haploidentical BMT. Conclusion: The evolution of a BMT program has a long learning curve and the expanded pool of eligible donors has led to a situation of "transplant for all". Haploidentical HSCT for nonmalignant hematological disorders is an unmet need. CART cell therapy and Cellular therapies need to be prioritized for future inclusion.

Sweetness and positivity together aren't a happy ending: Case controlled study amongst severe COVID-19 for impact of diabetes mellitus on survival.

Background: India is the epicenter of diabetes mellitus (DM). The relationship between COVID and DM in age/gender-matched non-diabetics has not been studied yet. The role of DM in predicting the disease severity and outcome in COVID patients might provide new insight for effective management. Methods: We conducted a prospective comparative study at a COVID care center from 25th April-31st May 2021. Among 357 severe-COVID patients screened, all consecutive diabetes (n-113) and age/gender-matched non-diabetes (n-113) patients were recruited. All diabetics and non-diabetics at admission were subjected to high resolution computed tomography (HRCT) chest and inflammatory markers (C-reactive protein (CRP), D-dimer, ferritin, interleukin-6 (IL-6), lactate dehydrogenase (LDH), Neutrophil-Lymphocyte Ratio (NLR)) before starting anti- COVID therapy. Statistical analysis was done using JMP 15·0 ver·3·0·0. Results: The prevalence of DM among the screened population (n-357) was 38·37%. The mean age of the study population was 61y with male preponderance (57%). There was no statistical difference in the HRCT-score or inflammatory markers in the two groups except for higher NLR (p-0·0283) in diabetics. Diabetics had significantly inferior overall survival (OS) (p-0·0251) with a 15d-OS of diabetics vs. non-diabetics being 58·87%, 72·67%, and 30d-OS of diabetics vs. non-diabetics being 46·76%, 64·61%, respectively. The duration of the hospital stay was not statistically different in the two groups (p-0·2). Conclusion: The mortality is significantly higher in severe-COVID patients with DM when compared to age/gender-matched non-diabetics. There was no significant difference in most inflammatory markers/CT at admission between the two groups.

Radiographical Spectrum of High-altitude Pulmonary Edema: A Pictorial Essay.

BACKGROUND: High-altitude pulmonary edema (HAPE) is a common cause of hospitalization in high altitude areas with significant morbidity. The clinical presentation of HAPE can overlap with a broad spectrum of cardiopulmonary diseases. Also, it is associated with varied radiological manifestations mimicking other conditions and often leading to unnecessary and inappropriate treatment. PATIENTS AND METHODS: The primary aim of the study was to study the various radiological manifestations of HAPE through real-world chest radiographs. We present six different chest X-ray patterns of HAPE as a pictorial assay, at initial presentation, and after the resolution of symptoms with supplemental oxygen therapy and bed rest alone. RESULTS: HAPE can present as bilateral symmetrical perihilar opacities, bilateral symmetrical diffuse opacities, unilateral diffuse opacities, bilateral asymmetrical focal opacities, and even lobar consolidation with lower zone or less commonly upper zonal predilection. These presentations can mimic many common conditions like heart failure, acute respiratory distress syndrome, pulmonary embolism, aspiration pneumonitis, pneumonia, malignancy, and tuberculosis. CONCLUSION: A holistic clinical-radiological correlation coupled with analysis of the temporal course can help high-altitude physicians in differentiating true HAPE from its mimics. HOW TO CITE THIS ARTICLE: Yanamandra U, Vardhan V, Saxena P, Singh P, Gupta A, Mulajkar D, et al. Radiographical Spectrum of High-altitude Pulmonary Edema: A Pictorial Essay. Indian J Crit Care Med 2021;25(6):668-674.

Targeted gene expression study using TaqMan low density array to gain insights into venous thrombo-embolism (VTE) pathogenesis at high altitude.

Venous thrombo-embolism (VTE) is multi-factorial disease involving several genetic and acquired risk factors responsible for its onset. It may occur spontaneously upon climbing at High Altitude (HA). Several studies demonstrated that hypoxic conditions prevailing at HA pose an independent risk factor for VTE; however, molecular mechanism remains unknown. Present study aims to identify genes associated with HA-induced VTE pathophysiology using real time TaqMan Low-Density Array (TLDA) of known candidate genes. Gene expression of total 93 genes were studied and analyzed in patients of VTE from HA (HA-VTE) and from sea level (SL-VTE) in comparison to respective controls. Both HA-VTE and SL-VTE patients showed up-regulation of 37 genes involved in blood coagulation cascade, clot formation, platelet formation, endothelial response, angiogenesis, cell adhesion and calcium channel activity. Seven genes including ACE, EREG, C8A, DLG2, USF1, F2 and PCDHA7 were up-regulated in both HA-controls and VTE patients (both HA-VTE and SL-VTE) indicating their role during VTE event and also upon HA exposure. Ten genes; CDH18, FGA, EDNBR, GATA2, MAPK9, BCAR1, FRK, F11, PCDHA1 and ST8SIA4 were uniquely up-regulated in HA-VTE. The differentially expressed genes from the present study could be determining factors for HA-VTE susceptibility and provide insights into VTE occurrence at HA.

Erythropoietin and ferritin response in native highlanders aged 4-19 years from the Leh-Ladakh region of India.

The pivotal role of erythropoietin (EPO) in hypoxic adaptation has led to various studies assessing the EPO and ferritin response in native highlanders from Andes and Tibet. We assessed the relationship between EPO, haemoglobin and ferritin in 335 native highlanders (172 boys and 163 girls, aged 4 to 19 years) from Leh-Ladakh, India, who had no history of travel to lowland areas. Complete blood counts, serum EPO and ferritin levels were measured. We stratified study subjects based on age, gender, pubertal status and analysed the EPO and ferritin levels between the stratified groups respectively. The mean EPO level in boys was lower than girls. The mean ferritin level in boys was significantly higher (P = 0·013) than in girls. There was no significant variation in the EPO and ferritin levels amongst the various age groups in our study. Near normal EPO levels since childhood with a negative correlation with haemoglobin is suggestive of a robust adaptive mechanism to high altitude from the early years of life. Low ferritin levels are indicative of decreased iron stores in these native highlanders.

High-altitude pulmonary oedema: Newer treatment modalities for an age-old problem.

Background & objectives: High-altitude pulmonary oedema (HAPE) continues to challenge the healthcare providers at remote, resource-constrained settings. High-altitude terrain itself precludes convenience of resources. This study was conducted to evaluate the rise in peripheral capillary saturation of oxygen (SpO2) by the use of a partial rebreathing mask (PRM) in comparison to Hudson's mask among patients with HAPE. Methods: This was a single-centre, randomized crossover study to determine the efficiency of PRM in comparison to Hudson's mask. A total of 88 patients with HAPE referred to a secondary healthcare facility at an altitude of 11,500 feet from January to October 2013 were studied. A crossover after adequate wash-out on both modalities was conducted for first two days of hospital admission. All patients with HAPE were managed with bed rest and stand-alone oxygen supplementation with no adjuvant pharmacotherapy. Results: The mean SpO2on ambient air on arrival was 66.92±10.8 per cent for all patients with HAPE. Higher SpO2values were achieved with PRM in comparison to Hudson's mask on day one (86.08±5.15 vs. 77.23±9.09%) and day two (89.94±2.96 vs. 83.39±5.93%). The difference was more pronounced on day one as compared to day two. Interpretation & conclusions: Mean SpO2values were found to be significantly higher among HAPE patients using PRM compared to those on Hudson's mask. Further studies to understand the translation of this incremental response in SpO2to clinical benefits (recovery times, mortality rates and hospital stay) need to be undertaken.

PRES in Pediatric HSCT: A Single-Center Experience.

Posterior reversible encephalopathy syndrome (PRES) has diverse etiologies and is closely linked to hematopoietic stem cell transplant (HSCT). Headache and seizures are the most common clinical presentations. Although near total recovery is seen in the majority of patients with appropriate management, the implications of its occurrence in the setting of an HSCT is much more than the residual neurological deficits. Graft rejection and occurrence of graft versus host disease has been reported. We analyzed retrospectively our data of 35 pediatric HSCT recipients over the last 2 years at our center. In total, 17% (n=6) patients developed PRES. Headache and seizures were the most common clinical presentations. All patients were on calcineurin inhibitors at the onset of symptoms. The median time after HSCT to the onset of PRES was 21 days. In total, 34% (n=2) patients developed residual neurological deficit. One patient died of acute graft versus host disease at a later date, and 50% (n=3) patients had graft rejection and return to transfusion dependence. The implications of PRES on HSCT outcomes are grave, and better immunosuppression transition protocols need to be developed.

A Case of Autosplenectomy in Sickle Cell Trait Following an Exposure to High Altitude.

A 24-year-old man presented with acute abdominal pain upon ascent to moderate altitude (3500 m). An immediate evaluation revealed a splenic infarct, and he was evacuated to sea level. Upon recovery, he was sent back to 3500 m without detailed etiological evaluation, whereupon he experienced recurrent episodes of left-side subcostal pain. Imaging suggested autosplenectomy, and workup revealed a negative thrombophilia profile but was positive for sickle cell trait (SCT). Individuals with SCT can be asymptomatic until exposure to severe hypoxia, upon which they can manifest clinically as sickle cell syndrome. We discuss the rare presentation of autosplenectomy in a patient with previously undiagnosed SCT on exposure to high altitude.

Comparison of Optic Nerve Sheath Diameter between both eyes: A Bedside Ultrasonography Approach.

CONTEXT: Optic nerve sheath diameter (ONSD) has long been accepted as a reliable proxy of intracranial pressure especially in critical care and bedside settings. The present consensus is to measure ONSD in both eyes and take average value, which is cumbersome and a potential cause of discomfort to the patient. AIM: We aim to compare the values of ONSD of the right and left eye in a random sample as measured by bedside ocular ultrasonography (USG) in Indian adults. SETTINGS AND DESIGN: This was a prospective study conducted from September 2012 to March 2013 in the Department of Internal Medicine of a tertiary care hospital situated at moderate high altitude (11,500 ft) in India. MATERIALS AND METHODS: Patients admitted with high altitude pulmonary edema (HAPE) were recruited by convenience sampling. The ONSD of both eyes were measured 3 mm behind the globe using a 7.5 MHz linear probe on the closed eyelids of supine subjects. STATISTICAL ANALYSIS: Analysis was done using SPSS 17.0. RESULTS: A total of 47 patients of HAPE were recruited to the study with daily ONSD recording of both eyes during the admission period. The mean ONSD of the left eye was 4.60 (standard deviation [SD] = 0.71) whereas the mean ONSD of right eye 4.59 (SD = 0.72). The ONSD of the right eye and left eye was strongly correlated (correlation coefficient = 0.98 with P < 0.0001). The mean difference in the ONSD of both eyes (right-left) was -0.0044 (SD = 0.11) which was not statistically significant (P = 0.533). CONCLUSION: Our results suggest that the difference in ONSD of both eyes is not statistically significant in disease or health. This study also suggests that the ONSD of either eye can be predicted by the other eye recordings. Based on these findings, it can be suggested that during ocular USG for routine bedside/research purposes it is sufficient to measure ONSD of any of the one eye to save time and avoid discomfort to the patient.

Endothelial markers in high altitude induced systemic hypertension (HASH) at moderate high altitude.

BACKGROUND: Chronic intermittent hypoxia is known to induce systemic arterial hypertension whereas chronic hypoxia causes pulmonary arterial hypertension. High altitude (HA) induced systemic hypertension (HASH) in previously normotensive lowlanders following acclimatisation and prolonged stay at moderate HA is a commonly encountered medical problem. HASH has been attributed to increased sympathetic discharge. Endothelial dysfunction (ED) is implicated in hypertension in the plains hence this study was conducted in HA. This is relevant especially because of the established role of ED in the aetiopathogenesis of HA illnesses. Since hypoxia may induce ED, we aimed at studying the association of endothelial dysfunction with HASH in temporary residents at HA. METHODS: In this case-control single-centre study, we evaluated ED, by measuring endothelial molecular markers, soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (VCAM-1), vascular endothelial growth factor (VEGF) and endothelial selectin (E-Selectin) in 24 cases with HASH and 25 age, sex matched normotensive controls at moderate high altitude (11,500 ft). RESULTS: The levels of sICAM-1 (patients: 214.3 ± 34.2 µg/L, controls: 196.2 ± 28.5 µg/L; p = 0.049) and VCAM-1 (patients 766.1 ± 123.4 ng/mL, controls: 668.6 + 117.6 ng/mL; p = 0.007) were statistically higher in the patient group. However, VEGF and E-Selectin were not significantly different between the groups. sICAM-1 significantly correlated with levels of systolic and diastolic blood pressure (r = 0.401, p = 0.003 and 0.486, p = 0.000) respectively. CONCLUSION: HASH is associated with endothelial dysfunction in form of raised levels of sICAM-1 and VCAM-1.