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.

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.

Bleeding risk assessment in immune thrombocytopenia.

The bleeding risk in immune thrombocytopenia (ITP) is related not only to low platelet count but also to the presence of platelet dysfunction. However, diagnosing a concomitant platelet dysfunction is challenging as most of the available platelet function assays (PFAs) require a platelet count of greater than 100,000/µL. Sonoclot coagulation and platelet function analyzer works on the principle of viscoelastometry, and results remain unaffected by the platelet counts. To assess the platelet function in adult acute ITP patients with the help of sonoclot coagulation and platelet function analyzer and correlate it with the risk of bleeding. Newly diagnosed acute ITP patients with a platelet count less than 20,000/µL were divided into two groups based on WHO bleeding grade: ITP non-bleeder (ITP-NB) group (WHO bleeding grade ≤1) and ITP bleeder (ITP-B) group (WHO bleeding grade ≥2). Platelet function was assessed by sonoclot in both groups. The patients without significant bleeding (ITP-NB) were followed up monthly for six months with the assessment of platelet function during each contact. Eighty patients (30 ITP-B and 50 ITP-NB) were prospectively included in this study. The median age of patients in the two groups was 37 years and 30 years, respectively. The female-to-male ratio was 4:1 and 1:1 in ITP-B and ITP-NB groups. The median platelet count in ITP-B and ITP-NB was 12000/µL (range 1000-19000/µL) and 8000/µL (range 1000-19000/µL), respectively. Mean platelet functions by sonoclot in both groups were lower than the normal cut-off (>1.6). However, the mean platelet function in the ITP-B group (0.2 + 0.17) was significantly lower than the ITP-NB group (1.2 ± 0.52) (p = 0.01). During the follow-up period of 6 months, patients in ITP-NB with a normal platelet function (>1.6) on sonoclot had lesser episodes (one episode) of clinically significant bleeding than patients with a low platelet function (4 episodes). Patients with acute severe thrombocytopenia and bleeding phenotype have a greater abnormality on platelet function by sonoclot than patients with non-bleeding phenotype. This information may help in taking therapeutic decisions in patients with acute ITP.

Clinico-laboratory Profile and Outcomes of Megaloblastic Anemia presenting as Severe Pyrexial Illness mimicking Tropical Infection.

BACKGROUND: Anemia-causing fever has been described in patients with megaloblastic anemia. Although the exact mechanism of this is unknown, high-grade fever is relatively less reported. MATERIALS AND METHODS: This prospective observational study included all new cases of megaloblastic anemia presenting with febrile illness (>101°F) during a 3-year period. Patients with existing anemia, comorbidities, and other causes of macrocytosis were excluded. A detailed evaluation for megaloblastic anemia and workup for excluding tropical infections was done. The patients were treated with parenteral vitamin B12, folic acid, and other hematinics. RESULTS: Around 24 cases of megaloblastic anemia presenting with high-grade fever were included, with 14 (58.3%) males, mean duration of fever 7.7 days (4-18 days), and 09 (37.5%) having temperature >103°F. The mean hemoglobin (Hb) was 8.15 g/dL (3.7-11.1 g/dL), the mean corpuscular volume (MCV) was 111 ± 7.8 fL, 18 (75%) had unconjugated hyperbilirubinemia, the mean lactate dehydrogenase (LDH) was 814 ± 24 IU/L, and 21 (87.5%) had low B12 or folate levels. Most showed good therapeutic response to B12 or folic acid with defervescence in 1-5 days (mean 2.6 days) and improvement in lab parameters in 1 week. The study population was divided into those with temperature ≥103°F, and temperature <103°F it was seen that there was a significant association (p < 0.05) with leucocyte count of ≤3000/cumm, and MCV ≥110 fL, in patients with temperature ≥103°F Conclusion: Megaloblastic anemia should be considered in the differentials of a patient presenting with a febrile illness with no clinical localization and a negative initial fever workup. Early identification and prompt therapy of this easily treatable disorder are very essential.

18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Scan Findings in a Rare Case of Subcutaneous Panniculitis-Like T-Cell Lymphoma.

Skin lymphomas are less common and subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a fairly rare subtype of primary cutaneous lymphoma. Skin lymphomas involve subcutaneous adipose tissues with no involvement of lymph nodes. Diagnosis of these cases is generally a challenge to clinicians. These cases present with fever, weight loss, and local discomfort in the region of involvement of subcutaneous tissues and sometime with skin eczema and rashes. Positron emission tomography/computed tomography (PET/CT) scan can guide in determining the extent of involvement being whole-body imaging and can guide the site of biopsy and can help to prevent misdiagnosis. It also helps in correct and early diagnosis and successful treatment. We report a case of a young adult who presented with pyrexia of unknown origin in which PET/CT scan revealed mildly fluorodeoxyglucose-avid diffuse subcutaneous panniculitis involving the whole body, trunk, and extremities. Biopsy was taken from the most appropriate site according to the PET/CT scan report and reported as SPTCL.

Supplemental Pioglitazone to Patients of CML with Suboptimal TKI Response: A Pragmatic Pilot Study.

Tyrosine kinase inhibitors (TKIs) have improved outcomes of chronic myeloid leukemia (CML). However, 20-30% of patients require second-line TKIs following suboptimal response. The cost and adverse events limit their use in resource-constraint settings. We conducted a pilot study to ascertain the benefit of adding pioglitazone to TKIs with suboptimal response in real-world resource-constraint settings. In this pragmatic pilot study from 01 Jan 2017 to 31 July 2021, CML patients from a tertiary care center in North India with sub-optimal response to TKIs were additionally given pioglitazone after ruling out imatinib resistance mutation (n - 31). Pioglitazone was stopped if there was disease progression on follow-up, and second-line TKI was started. The data were analyzed with the intention-to-treat principle using JMP Ver.15.1.1. The median age of the study population was 54y (27-82), who were followed up for a median duration of 1023.5d (59-1117). Pioglitazone showed the benefit of one-log reduction in BCR-ABL in 89.7% of the study participants. 1y, 2y and 3y-PFS were 92.57%, 76.5%, and 68.3% respectively. During follow-up period, the disease progressed in 38.7%, of which two succumbed. No adverse events to Pioglitazone were documented. This study proved that adding Pioglitazone to the existing TKI regime in CML with sub-optimal response can benefit. The addition of Pioglitazone was well tolerated. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-022-01561-x.

Role of Matrix Degradation, Oxidative Stress, Inflammation & Trace Elements in COVID-19 Patients: A Multivariate Study from India.

The interrelationship between matrix degradation, oxidative stress, inflammation and trace elements can be speculated in COVID-19. The objective of the study was to evaluate the oxidative stress, inflammation and matrix degradation markers and trace elements in COVID-19 positive patients. A group of confirmed severe COVID-19 positive patients (n = 30) along with COVID-19 negative patients (n = 30) with similar symptoms were included. Both group of patients were assessed for oxidative stress markers, inflammatory cytokines, matrix metalloproteinase (MMP)s and their inhibitors along with trace elements in blood. All the data were subjected to univariate as well as multivariate analysis including PCA, PLS-DA, OPLS-DA. Diagnostic accuracy was tested by ROC curve analysis. Further relationship with Neutrophil/ lymphocyte (N/L) ratio was established if any. Increased oxidative stress, inflammation and matrix degradation is evidenced by significant rise in oxidative markers, inflammatory cytokines and MMP9/TIMP-1 ratio. Decreased Cu/Zn ratio is also observed in COVID-19 positive patients. Multivariate analysis identified SOD, Cu/Zn ratio, IL-6 and TOS, as effective discriminant among the two groups of patients. Further, accuracy was confirmed by ROC curves. Neutrophil/ lymphocyte (N/L) ratio, shows significant negative association with SOD (r= -0.75, p < 0.005) and Cu/Zn ratio (r = -0.88, p < 0.005). These data suggest the attributes of these biomarkers in disease severity. The potential use of these blood-based laboratory markers in disease prognosis seems promising and warrants further attention. Given by the symptoms and severity of the disease, it will be promising to monitor Cu/Zn ratio along with other prognostic indicators.

Transcriptome Analysis of Developing Grains from Wheat Cultivars TAM 111 and TAM 112 Reveal Cultivar-Specific Regulatory Networks.

Wheat flour's end-use quality is tightly linked to the quantity and composition of storage proteins in the endosperm. TAM 111 and TAM 112 are two popular cultivars grown in the Southern US Great Plains with significantly different protein content. To investigate regulatory differences, transcriptome data were analyzed from developing grains at early- and mid-filling stages. At the mid-filling stage, TAM 111 preferentially upregulated starch metabolism-related pathways compared to TAM 112, whereas amino acid metabolism and transporter-related pathways were over-represented in TAM 112. Elemental analyses also indicated a higher N percentage in TAM 112 at the mid-filling stage. To explore the regulatory variation, weighted correlation gene network was constructed from publicly available RNAseq datasets to identify the modules differentially regulated in TAM 111 and TAM 112. Further, the potential transcription factors (TFs) regulating those modules were identified using graphical least absolute shrinkage and selection operator (GLASSO). Homologs of the OsNF-Y family members with known starch metabolism-related functions showed higher connectivities in TAM 111. Multiple TFs with high connectivity in TAM 112 had predicted functions associated with ABA response in grain. These results will provide novel targets for breeders to explore and further our understanding in mechanisms regulating grain development.

Effect of treatment regimens in severe COVID pneumonia at an Indian tertiary care hospital: An observational, real-world study.

Background: Corticosteroids have attracted attention as a treatment option for severe Coronavirus disease (COVID-19). However, published data on steroid therapy is debatable, and real-world data is lacking. This study evaluated the effect of treatment regimens, especially Pulse steroid therapy (Injection Methyl Prednisolone 250 mg iv once a day for three days) in severe-COVID-19 pneumonia at an Indian tertiary care hospital. Methods: This observational cross-sectional study included severe COVID-19 pneumonia patients aged >18 years, requiring assisted ventilation. As part of the hospital protocol, patients received either pulse steroid therapy, remdesivir or tocilizumab in addition to the recommended steroid doses i.e., injection of dexamethasone 6 mg iv once a day. The association of factors and treatment regimens to patient outcomes was evaluated. Results: Data of eighty-three patients were assessed, majority being above 60 years (n = 30, 36.14%) and males (n = 45/83, 54.21%). The commonest comorbidities were hypertension (n = 26), diabetes (n = 23) and obesity (n = 19), fifty-five patients (66.26%) reported at least one comorbidity. Sixty-one patients (73.49%) had received pulse steroid regimen, forty-eight patients (57.83%) were administered remdesivir-based regimen while twelve patients (14.46%) had received tocilizumab treatment. 54.1% patients managed with pulse steroid regimens were discharged after treatment, statistically similar to remdesivir-managed subgroup (62.5%, p > 0.05). On sub-group analysis, pulse steroids showed better outcomes in young males with no comorbidities. No comorbidity had significant relationship with patient outcomes (p > 0.05). Conclusion: Pulse steroid therapy is an effective therapy in management of patients with severe COVID-19 pneumonia in a real-world setting, with better outcomes in young males without comorbidities. Pulse steroids can be considered a viable option for severe-COVID-19 pneumonia management.

Cancer in the Adolescent and Young Adults (AYA) and Children: A Comprehensive Analysis of the Epidemiology and Psychosocial Morbidity in the Indian Population.

Bhupesh GuleriaAims Adolescent and young adults (AYAs), children with cancer, and their guardians have unique psychosocial morbidities adversely effecting quality of life (QOL). This is measurable using patented tools. We analyzed epidemiological and clinicopathological patterns of solid organ cancers in this subgroup. We also assessed psychosocial morbidity and changes in QOL faced by them. Methods All patients aged 2 to 39 years, newly diagnosed with cancer from April 2017 to March 2019 were included. Clinical history, diagnosis, staging, treatment, outcomes, and follow-up were recorded. The National Comprehensive Cancer Network (NCCN) distress thermometer and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ C-30) were used to assess psychosocial morbidity of AYAs, children ≥ 12 years, and parents of children < 12 years. Pediatric Quality of Life Inventory (Peds QL) version 3.0 was used for children < 12 years. Data was analyzed using descriptive statistics. Results A total of 571 patients (512 AYAs, 59 children) were enrolled. Median age was 30 years with male predominance (58.1%). Most cases (98.6%) were absent from school or work. Carcinoma breast was the most common in females (29.3%) and non-Hodgkin lymphoma in males (12.6%). 91.06% had overall NCCN distress score ≥ 4. Also, 73.81 and 79.49% had "quite a bit" or "very much" responses on functional and symptom scales, respectively, in EORTC QLQ C-30 questionnaire. Peds QL version 3.0 revealed total score ranging from 276 to 523 for each patient. Conclusion AYAs and children with cancer are extremely vulnerable to psychological stress and morbidity. Use of well-established tools help in assessing their mental status and timely psychiatric referral can be initiated.

Disease profile and patient outcomes in vaccinated COVID-19 patients at a tertiary care Indian hospital: An observational, real-world study.

Background: There is a lack of real-world evidence evaluating the disease outcomes and patient features in vaccinated coronavirus disease (COVID-19) cases. This study aimed to address this scientific need gap and also compare characteristics between the partially vaccinated and fully vaccinated COVID-19 patients in India. Methods: This observational cross-sectional study included data of adult patients diagnosed with COVID-19 at a tertiary care Indian hospital with a history of at least single-dose COVID-19 vaccination. Overall evaluation of patient features and disease characteristics was done. Patients were segregated into two groups based on vaccination status (partial or fully vaccinated), and characteristics were compared between these two groups along with COVID-19 outcomes. Results: Data of 403 vaccinated patients treated for breakthrough COVID-19 infection postvaccination was evaluated. The mean age was 47.7 ± 15.3 years (range: 19-87 years), with the majority being males (73.94%); 54.1% of evaluated cases were fully vaccinated; 74.93% of cases were asymptomatic. The majority of the symptomatic cases (60.39%) suffered from only mild-moderate symptoms; 72.7% of cases needed only home isolation, while only 1.99% died. A significantly higher number of partially vaccinated COVID-19 patients had severe COVID-19 pneumonia vs. fully vaccinated ones (14.59% vs. 5.96%, p < 0.05). The relative risk (RR) for the development of severe COVID-19 infection was 0.32 for the fully vaccinated subgroup, which was a significant finding (CI: 0.19-0.55, p < 0.05). Conclusion: The majority of vaccinated COVID-19 patients are asymptomatic or suffer from mild clinical features, which can be managed with home isolation. Fully vaccinated patients have a lower risk of developing severe COVID-19 infection in comparison to partially vaccinated cases.

Real-world experience of anti-D immunoglobulin in immune thrombocytopenia.

In developing countries, anti-D has been used in immune thrombocytopenia (ITP) as a cheaper alternative to human immunoglobulin. We aim to analyze the response and safety profile of anti-D in patients with severe ITP. A retrospective study was conducted at a tertiary care hospital in Northern India. Patients received a single intravenous infusion of 75 µg/kg anti-D. In total, 36 patients (20 females) were included in this study. The median duration from ITP diagnosis to anti-D therapy was 235 days (range 1-1613 days). Four (11.1%) patients received anti-D as an upfront treatment. The patients' platelet counts rose significantly by the end of day three and continued to be significantly high until day 30 of receiving anti-D (p ≤ 0.001). The overall response rate (ORR) by day seven was 88.89%. There was no effect of age, sex, duration of disease, prior therapy, and platelet count on the ORR. Patients were followed up for a median duration of 52 days (longest follow-up: 3080 days). Six (6/36, 16.67%) patients continued to be in remission till the last follow-up. The hemoglobin fall was statistically significant on day three and day seven (p < 0.001 and p = 0.001) and got normalized by day 30. We observed equally good ORR in mixed populations and different phases of ITP along with long-term sustained response. The study demonstrates a quick and high response rate along with good safety profile to anti-D in all forms of ITP.

Anemia in cirrhosis: An underestimated entity.

Anemia in a patient with cirrhosis is a clinically pertinent but often overlooked clinical entity. Relevant guidelines highlight the algorithmic approach of managing a patient of cirrhosis presenting with acute variceal hemorrhage but day-to-day management in hospital and out-patient raises multiple dilemmas: Whether anemia is a disease complication or a part of the disease spectrum? Should iron, folic acid, and vitamin B complex supplementation and nutritional advice, suffice in those who can perform tasks of daily living but have persistently low hemoglobin. How does one investigate and manage anemia due to multifactorial etiologies in the same patient: Acute or chronic blood loss because of portal hypertension and bone marrow aplasia secondary to hepatitis B or C viremia? To add to the clinician's woes the prevalence of anemia increases with increasing disease severity. We thus aim to critically analyze the various pathophysiological mechanisms complicating anemia in a patient with cirrhosis with an emphasis on the diagnostic flowchart in such patients and proposed management protocols thereafter.

Immune Thrombocytopenia in a Kidney Transplant Recipient Treated with Romiplostim.

We present a case of immune thrombocytopenia following a living donor kidney transplant. Thrombocytopenia started two days after transplant and continued up to seven weeks after transplant, despite an extensive workup, treatment with steroids, intravenous immune globulin, and alterations in immunosuppression and other medications. In the absence of platelet transfusions, the patient's platelet count remained < 20,000/mm3. Platelet count responded to romiplistim (Nplate®, Amgen Inc.) within two weeks and has remained stable for twelve months after initiation of this agent. The patient's graft function has also been stable. This experience suggests romiplostim is safe and effective for persistent immune thrombocytopenia in kidney transplant recipients.

Tissue specific expression of UMAMIT amino acid transporters in wheat.

Wheat grain protein content and composition are important for its end-use quality. Protein synthesis during the grain filling phase is supported by the amino acids remobilized from the vegetative tissue, the process in which both amino acid importers and exporters are expected to be involved. Previous studies identified amino acid importers that might function in the amino acid remobilization in wheat. However, the amino acid exporters involved in this process have been unexplored so far. In this study, we have curated the Usually Multiple Amino acids Move In and out Transporter (UMAMIT) family of transporters in wheat. As expected, the majority of UMAMITs were found as triads in the A, B, and D genomes of wheat. Expression analysis using publicly available data sets identified groups of TaUMAMITs expressed in root, leaf, spike, stem and grain tissues, many of which were temporarily regulated. Strong expression of TaUMAMITs was detected in the late senescing leaves and transfer cells in grains, both of which are the expected site of apoplastic amino acid transport during grain filling. Biochemical characterization of selected TaUMAMITs revealed that TaUMAMIT17 shows a strong amino acid export activity and might play a role in amino acid transfer to the grains.

Near-Miss Incidents in Obstetric Patients Admitted to an Intensive Care Unit of a Tertiary Care Center in Eastern India: A Retrospective Cohort Study.

Aim: Obstetric patients presenting to the intensive care units (ICU) with or without underlying medical or surgical comorbidities can be a challenge to both the treating obstetrician and the intensivist. They occasionally present with near-miss events which if left untreated, can result in death. Objectives: To study the prevalence, indications of ICU admissions, near-miss events, and their effect on mortality in obstetric and puerperal patients. Material & methods: We conducted a retrospective analysis of the health records of all the obstetric and puerperal patients (pregnant and until 6 weeks postpartum) admitted to our tertiary care hospital from January 2019 to December 2020. Patient demographic characteristics, obstetric, surgical, and medical conditions, acute physiology, and chronic health evaluation (APACHE) II scores, organ failures, treatment, ICU and hospital length of stay, and mortality outcomes were studied. Results: A total of 22 obstetric patients were admitted to the ICU during the above study period. Mean age was 28.7 ± 6.24 years, mean gestation was 34.4 ± 6.61 weeks, mean APACHE II score was 12.68 ± 5.67, median ICU length of stay was 5 days, and median duration of hospital length of stay was 10 days. The antepartum risk factors such as severe preeclampsia (27%), antepartum bleeding (14%), and postpartum complications like postpartum haemorrhage (33%), sepsis with multiorgan failure (25%) are the commonest indications that resulted in ICU admission. Conclusion: Higher APACHE II scores at the time of ICU admission, prolonged ICU, and hospital length of stay may be associated with high maternal mortality.

Safety and efficacy of splenectomy in immune thrombocytopenia.

BACKGROUND: Immune Thrombocytopenia (ITP) is characterized by low platelet counts. Splenectomy has been in practice for the treatment of ITP since the early 20th century. We aimed to analyze the data of ITP patients from our hospital who underwent splenectomy and further present the long-term outcome and safety profile in these patients. METHOD: This study was a single-center, registry based study conducted at a tertiary care hospital in Northern India. Patients aged 18 years or more, who underwent splenectomy after at least one line of therapy, were included in the study. The primary outcome was the overall response rate (ORR) at one month after splenectomy. Secondary outcomes were sustained response, relapse-free survival, factors affecting the ORR, and adverse events after splenectomy. RESULTS: Forty-five patients of ITP were included in the study. Thirty-six patients underwent splenectomy in the first half (2001-2010), of the study period. The median age of the patients was 38 (19-56) years. The median duration from diagnosis to splenectomy was 1.76 (0.47-2.58) years. The median number of therapy received before splenectomy was 3 (1-6). The overall response rate (ORR) post-splenectomy at day 30 was 89.2% with 61.8% complete response (CR). The ORR was 88.5% at 1-year, with 48.8% CR. The relapse-free survival (RFS) at 5-years was 57.38% (95% Confidence Interval 40.59-71.02%), There was no effect of duration of disease, age, gender, and prior therapy received, on the ORR at one-month. At one year, the platelet response was significantly better in patients who had a CR at one-month than patients who had a partial response at one month. The relapse-free survival was better in patients who achieved CR after 1-month of splenectomy. During the median follow-up of 5.02 (1 month-20 years) years, there were five cases of overwhelming post-splenectomy infection (OPSI). There was no recorded incidence of perioperative mortality, deep vein thrombosis, or mesenteric thrombosis. DISCUSSION: Despite the variation in outcome from different studies, splenectomy gives the best possible long-term treatment-free remission amongst all the available second-line agents. It is also, one of the most financially affordable therapies. Despite advantages, the number of ITP patients undergoing splenectomy has been on the decline and largely attributable to the newer and more effective second-line therapies. There is no pre-surgery variable predicting the ORR after splenectomy. CONCLUSION: Splenectomy in ITP offers a long-term sustained response at an economical cost.