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Objectives: To report the outcomes of pediatric patients who underwent allogeneic hematopoietic stem cell transplant (HSCT) in single rooms without high-efficiency particulate air (HEPA) filters, laminar air flow or positive pressure at our centre and discuss the adaptations of a high-volume government centre. Methods: Data of the first 20 children who underwent allogeneic HSCT between May 2019 and July 2023 in adaptive settings were reviewed retrospectively. All patients were managed in in single rooms without HEPA filters, positive pressure or laminar air flow. Supportive care in the form of antimicrobial prophylaxis, veno-occlusive disease prophylaxis, anti-epileptics (with busulfan) and irradiated blood products were provided. Trained manpower including multi-specialty consultations were readily available. All complications including infections were managed as per standard guidelines. Results: The median (range) of children included was 6 (1–20) years. For eight patients we used alternate donors. The mean (SD) time to neutrophil and platelet engraftment were 17.0 (8.07) days and 18.8 (10.1) days, respectively. The mean (SD) time to discharge from the hospital was 30.9 (10.04) days. There were no deaths within 30 days. Six children each developed acute and chronic graft-versus-host disease (GVHD). The overall survival at a median follow-up of 292 days was 70% (n = 14). Conclusions: With certain adaptations in the existing infrastructure in resource-limited settings, allogeneic HSCT can be performed with good outcomes, provided experienced, dedicated and adequate personnel, comprehensive supportive care, multidisciplinary consultative support and isolation are provided. [ABSTRACT FROM AUTHOR]

Background: Despite the fundamental progress in hematopoietic stem cell transplant, this treatment is also associated with complications. Graft-versus-host disease is a possible complication of HSCT. Bronchiolitis obliterans syndrome (BOS) is the pulmonary form of this syndrome. Due to the high morbidity and mortality rate of BOS, various studies have been conducted in the field of drug therapy for this syndrome, although no standard treatment has yet been proposed. According to the hypotheses about the similarities between BOS and chronic obstructive pulmonary disease, the idea of using tiotropium bromide as a bronchodilator has been proposed. Method/design: A randomized, double-blind, placebo-controlled, and crossover clinical trial is being conducted to evaluate the efficacy of tiotropium in patients with BOS. A total of 20 patients with BOS were randomly assigned (1:1) to receive a once-daily inhaled capsule of either tiotropium bromide (KP-Tiova Rotacaps 18 mcg, Cipla, India) or placebo for 1 month. Patients will receive tiotropium bromide or placebo Revolizer added to usual standard care. Measurements will include spirometry and a 6-min walking test. Ethics/dissemination: This study was approved by the Research Ethics Committees of Imam Khomeini Hospital Complex, Tehran University of Medical Science. Recruitment started in September 2022, with 20 patients randomized. The treatment follow-up of participants with tiotropium is currently ongoing and is due to finish in April 2024. The authors will disseminate the findings in peer-reviewed publications, conferences, and seminar presentations. Trial registration: Iranian Registry of Clinical Trial (IRCT) IRCT20200415047080N3. Registered on 2022–07-12, 1401/04/21. [ABSTRACT FROM AUTHOR]

This study describes the profile of children diagnosed with posterior reversible encephalopathy syndrome (PRES) in the pediatric hematology oncology unit and highlights the clinical features of PRES in immunosuppressed children. This retrospective study included 10 children diagnosed with PRES with a mean age of 6.8 years. Acute lymphoblastic leukemia was the most common primary diagnosis followed by post-hematopoietic stem cell transplant patients. Most cases of PRES occurred within one month of treatment initiation. Hypertension was noted in all at the time of diagnosis. Neuroimaging revealed bilateral lesions with parietal and occipital lobe involvement being the most common. All patients received corticosteroids as part of treatment for primary diagnosis. Controlling blood pressure was critical in managing PRES. Consideration of PRES as a clinical possibility in pediatric hematology oncology unit in children presenting with symptoms such as headache, seizures, and visual disturbances will aid in early diagnosis after ruling out other causes of these symptoms. [ABSTRACT FROM AUTHOR]

Introduction. Due to the significant resources involved in creating HSCT programs there is a significant disparity in the availability of this treatment modality between the developed and developing countries. This manuscript details the process and the outcomes of the first HSCT program in East Africa which was started at Muhimbili National Hospital (MNH) in Dar-es-Salaam, Tanzania. Materials and Methods. Information and data were collected on the processes which had been implemented for starting the HSCT program at MNH. The details of the collaborations, training, infrastructure development, and acquisition of the biomedical equipment, as well as the actual process for HSCT, as well as the outcomes of treatment are described. Observations. The project has been detailed in 4 stages for ease of description: Stage 1: Preparatory work which was performed by the Government of Tanzania, as well as the administrators and clinicians from MNH (July 2017-September 2021). Stage 2: Exploratory gap analysis by the teams from MNH and International Haematology Consortium of HCG Hospital, India (HCG-IHC) in October 2021. Stage 3: Activities for closure of gaps (November 2021). Stage 4: Stem Cell Transplantation Camps (November 2021 to March 2022). 11 peripheral blood stem cell transplants were done in two camps, November 2021 (5 patients), and February 2022 (6 patients). 10 patients underwent autologous peripheral blood stem cell transplantation for multiple myeloma and 1 for lymphoma. The median duration of hospital stay was 19 ± 6 days. The median time for neutrophil engraftment, it was on 8.8 ± 0.8 days, and for platelet engraftment was 9.6 ± 2.4 days. Progression-free survival was 100%, and there was no mortality. Conclusion. Commonalities in the socioeconomic challenges in developing countries can be leveraged to create robust HSCT programs in other developing countries. [ABSTRACT FROM AUTHOR]

Objectives: Fecal microbiota transplantation (FMT) is an emerging option for recurrent or refractory Clostridium difficile-associated diarrhea (CDAD). We describe a single-center experience of FMT in hematopoietic stem cell transplant (HSCT) recipients with CDAD in India. Methods: A prospective observational study of HSCT recipients with CDAD who received FMT in our center. Results: A total of 13 patients were included. All the patients were allogenic HSCT recipients; FMT was performed in seven patients due to refractory CDAD, in five patients due to the presence of both CDAD and graft vs host disease (GVHD), and in 1 patient due to recurrent CDAD. The approach to FMT was colonoscopic in 10 (77%) patients. Only one patient reported bacteremia and one patient had candidemia, both of which were unrelated to FMT. Of the 10 patients who had complete resolution of CDAD, only one patient presented with a recurrence of CDAD within 8 weeks post-FMT. Conclusion: This is the first study from India using FMT as a therapeutic modality for CDAD in the setting of HSCT. Here we demonstrate that FMT in India is an effective option, especially when patients have refractory CDAD, recurrent CDAD, or both GVHD and CDAD. Further studies should explore the efficacy and feasibility of FMT in India. [ABSTRACT FROM AUTHOR]

Donor lymphocyte infusions (DLIs) are often recommended products after allogeneic hematopoietic stem cell transplant to increase graft - versus - leukemia effect. More success rate of DLI has been reported in relapsed posttransplant chronic myeloid leukemia. Whatever the indication for DLI, mortality related to post-DLI infusion is 5%-20%, and more than one-third of patients will develop acute and/or chronic graft versus host disease (GVHD) after DLI. We report two cases where DLIs were used for residual disease after posttransplant. Both of DLI went uneventful. None of the patient's developed signs of GVHD postinfusion. Although both patients expired with different causes, none were related to DLI infusion. Information from published literature suggests that DLI should be administered early after relapse or as a prophylactic strategy in patients receiving T-cell-depleted grafts, and patients with aggressive diseases may benefit from disease reduction before DLI. However, further evidence is required to evaluate its efficacy, especially in relapsed or residual hematological malignancies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment modality for a range of hematological disorders including malignancies. The increasing volumes of HSCTs impact transfusion services and the requirement of blood products vary depending on the primary disease, type and phase of transplant, and the HSCT donor type. MATERIALS AND METHODS: This study analyzed the factors affecting blood component requirements in patients undergoing HSCT. The authors studied the transfusion requirement of packed red blood cells (PRBC) and platelets (PLT) up to 100 days post-transplant among 617 adult patients undergoing HSCT during the study period (2007-2019). RESULTS: Requirement of PRBC and PLT was significantly higher (P < 0.05) in allogenic HSCT cases across all three phases of transplant compared to autologous HSCT. Unlike PRBC requirement, the PLT requirement was significantly higher during peri-transplant period for haploidentical HSCT and major ABO-incompatible HSCT group compared to matched related donor HSCT and ABO identical HSCT, respectively. In subset analysis based on diagnosis with leukemia as reference, the multiple myeloma group required less while the anemia group required more PRBC and PLT transfusions. The leukemia group required more PRBC than lymphoma group, while the PLT requirement was vice-versa. CONCLUSION: Factors such as allogeneic HSCT, haploidentical donor type, major ABO-incompatible HSCT, and primary diagnosis as leukemia or anemia were the predictors for increased need of blood products. As higher transfusion requirements may translate into increased costs of treatment, a study like this can help in managing blood component inventory and planning treatment costs of a HSCT program. [ABSTRACT FROM AUTHOR]

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) has emerged as a curative measure for life-threatening hematological disorders. It can be autologous or allogeneic depending on the disease characteristics. Providing transfusion support to the transplant patients can be challenging, especially in AB-mismatched allogeneic HSCT. In this study, we investigated the impact of ABO incompatibility in patients undergoing allogeneic HSCT. MATERIALS AND METHODS: A retrospective review was conducted in 76 patients with hematological diseases who underwent allogeneic HSCT. Transfusion requirements, engraftment profile, incidence of graft versus host disease (GvHD), and mortality for a period of 1 year were analyzed. RESULTS: ABO incompatibility between donor and the patient did not significantly affect the neutrophil and platelet (PLT) engraftment time (P = 0.389, 0.349, respectively), packed red blood cells transfusion requirement, and duration of initial hospital stay. However, patients of ABO-incompatible HSCT received more PLT transfusions posttransplant which was statistically significant. 29.1% of ABO compatible and 16.7% incompatible HSCT patients developed GVHD. Mortality rates in the two groups were 16.7% and 8.3%, respectively. However, differences in both the parameters were not statistically significant. CONCLUSION: Our study showed that ABO incompatibility does not significantly affect the outcome and should not be a limiting factor for selection of donor. Donor availability and human leukocyte antigen (HLA) matching remain the critical selection criteria. [ABSTRACT FROM AUTHOR]

DOCK8 deficiency affects various cell subsets belonging to both the innate and adaptive immune systems. Clinical diagnosis is challenging, as many cases present with severe atopic dermatitis as the only initial manifestation. Though flow cytometry helps in the presumptive diagnosis of DOCK8‐deficient patients by evaluating their DOCK8 protein expression, it requires subsequent confirmation by molecular genetic analysis. Currently, haematopoietic stem cell transplantation (HSCT) is the only curative treatment option available for these patients. There is a paucity of data from India on the clinical diversity and molecular spectrum of DOCK8 deficiency. In the present study, we report the clinical, immunological and molecular findings of 17 DOCK8‐deficient patients from India diagnosed over the last 5 years. [ABSTRACT FROM AUTHOR]

Introduction: Currently, there are no guidelines for the management of B-cell lineage acute lymphoblastic leukemia (B-ALL) from an Indian perspective. The diagnostic workup, monitoring, and treatment of B-ALL vary among different physicians and institutes. Objective: To develop evidence-based practical consensus recommendations for the management of B-ALL in Indian settings. Methods: Modified Delphi consensus methodology was considered to arrive at a consensus. An expert scientific committee of 15 experts fromIndia constituted the panel. Clinically relevant questions belonging to threemajor domains were drafted for presentation and discussion: (i) diagnosis and risk assignment; (ii) frontline treatment; and (iii) choice of therapy (optimal vs. real-world practice) in relapsed/refractory (R/R) settings. The questionnaire was shared with the panel members through an online survey platform. The level of consensus was categorized into high (= 80%), moderate (60%-79%), and no consensus (< 60%). The process involved 2 rounds of discussion and 3 rounds of Delphi survey. The questions that received near or no consensus were discussed during virtual meetings (Delphi rounds 1 and 2). The final draft of the consensus was emailed to the panel for final review. Results: Experts recommended morphologic assessment of peripheral blood or bone marrow, flow cytometric immunophenotyping, and conventional cytogenetic analysis in the initial diagnostic workup. Berlin-Frankfurt-Münster (BFM)-based protocol is the preferred frontline therapy in pediatric and adolescent and young adult patients with B-ALL. BFM/German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia-based regimen is suggested in adult patients with B-ALL. Immunotherapy (blinatumomab or inotuzumab ozogamicin) followed by allogeneic hematopoietic cell transplantation (allo-HCT) is the optimal choice of therapy that would yield the best outcomes if offered in the first salvage in patients with R/R B-ALL. In patients with financial constraints or prior allo-HCT (real-world practice) at first relapse, standard-intensive chemotherapy followed by allo-HCT may be considered. For subsequent relapses, chimeric antigen receptor T-cell therapy or palliative care was suggested as the optimal choice of therapy. Conclusion: This expert consensus will offer guidance to oncologists/clinicians on the management of B-ALL in Indian settings. [ABSTRACT FROM AUTHOR]

Introduction: Allogenic hematopoietic stem cell transplantation (HSCT) is the only curative treatment for hematologic malignancies. Nowadays, usually, haploidentical stem cell transplant is performed across the ABO blood group barrier; however, the effect of ABO incompatibility on haploidentical hematopoietic stem-cell transplantation is still uncertain. Methodology: Retrospective analysis of data of patients who underwent haploidentical hematopoietic stem-cell transplantation at our hospital was performed. The patient cohort was classified in to two arms: ABO compatible and ABO-incompatible haploidentical stem cell transplantation. ABO-incompatible was further categorized as major mismatch, minor mismatch and bidirectional mismatch. The average follow-up period was 6 months posttransplant for which the following parameters were studied: (a) engraftment kinetics for white blood cell (WBC) and platelets, (b) graft rejection, (c) overall graft survival, (d) graft-versus-host disease (GVHD), and (e) clinical variation in outcome for patients receiving peripheral blood stem cell/bone marrow harvest (BMH) as the source of stem cells. Results: The median age of recipients for both ABO compatible and ABO incompatible was 24 years and most of them were parent-offspring transplants. A total of 39 patients underwent haploidentical stem cell transplantation during the study period. Our cohort consisted of 23 ABO-compatible patients and 17 ABO incompatible patients. Out of these 17, 6 were major mismatch, 11 were minor mismatch and none were bidirectional mismatch. Of these 39 patients, 82% (32/39) engrafted within the normal expected time frame. The average days to WBC and platelet engraftment in these subgroups were noted to be as follows: Major - 12 and 18 days, compatible - 9 and 17 days, and minor - 10 and 17 days, respectively. Graft failure was observed in 20% (8/39) of patients, of which 4 patients had undergone ABO-compatible transplants while 4 patients had undergone minor ABO incompatible transplants. In this study, we observed that major ABO incompatibility had severe risk of GVHD (17%) compared to compatible (39%) and minor (27%) blood group mismatch. The overall survival rate in 6 months was equal (70%) in both arms. 5/39 patients, i.e., 12% received BMH as the source of stem cells, of these 80% are alive. Conclusion: Haploidentical transplants done in patients with ABO-incompatible donors had outcomes comparable to the ABO-compatible group. The risk of severe GVHD did not increased in the ABO mismatch group. Recipient of BMH had a marginally better graft survival. [ABSTRACT FROM AUTHOR]

Background: Sex disparity and its determinants in childhood cancer in India remain unexplored, with scarce information available through summary statistics of cancer registries. This study analysed the degree of sex bias in childhood cancer in India and its clinical and demographical associations.Methods: In this retrospective, multicentre cohort study, we collected individual data of children (aged 0-19 years) with cancer extracted from the hospital-based records of three cancer centres in India between Jan 1, 2005, and Dec 31, 2019, and two population-based cancer registries (PBCRs; Delhi [between Jan 1, 2005, and Dec 31, 2014] and Madras Metropolitan Tumour Registry [between Jan 1, 2005, and Dec 31, 2017]). We extracted data on age, sex, and confirmed diagnosis of malignancy (according to the International Classification of Diseases-10 coding),and excluded participants if they were without a recorded diagnosis, had a benign diagnosis, had missing sex information, resided outside of India, or were a donor for haematopoietic stem cell transplantation (HSCT). The primary outcome was the male-to-female incidence rate ratio (MF-IRR) in the two PBCRs and the male-to-female ratios (MFR) from the hospital-based and the HSCT data. For PBCR data, MF-IRR was estimated by dividing the MFR by the total population at risk. MFR was analysed for patients seeking treatment at the cancer centres and for those undergoing HSCT. Logistic regression analyses were done to explore the association of clinical and demographical variables with sex of the patients seeking treatment and those undergoing HSCT in hospital-based data and multivariable analyses were done to determine independent sociodemographic predictors of sex bias. Annual time trends of MFR and MF-IRR during the 15-year study period were ascertained by time series regression analyses.Findings: We included 11 375 children from PBCRs in the study. 26 891 children from hospital-based records were screened, and data from 22 893 (85·1%) were included (including 514 who underwent HSCT). Residence details were missing for 257 (1·1%) of 22 893 patients from hospital-based records. The crude MFR of children at diagnosis was in favour of boys: 2·00 (95% CI 1·92-2·09) in the Delhi PBCR and 1·44 (1·32-1·57) in Madras Metropolitan Tumour Registry. The MF-IRRs for cancer diagnosis were also skewed in favour of boys in both PBCRs (Delhi 1·69 [95% CI 1·61-1·76]; Madras Metropolitan Tumour Registry 1·37 [1·26-1·49]). The MFR for children seeking treatment from hospital-based records was 2·06 (95% CI 2·00-2·12) in favour of boys. In subgroup analyses, the proportion of boys seeking treatment was higher in northern India than southern India (p<0·0001); in private centres than in centres providing subsidised treatment (p<0·0001); in patients with haematological malignancies than those with solid malignancies (p<0·0001); in those residing 100 km or further from the hospital than those within 100 km of a hospital (p<0·0001); and those living in rural areas than those living in urban areas (p=0·0006). The MFR of 514 children who underwent HSCT was 2·81 (95% CI 2·32-3·43) in favour of boys. Time trend analysis showed that MFR did not show any significant annual change in either the overall cohort or in any of the individual centres for hospital-based data; however, the analysis did show a declining MF-IRR in the Delhi PBCR from 2005 to 2014 (p=0·031).Interpretation: The sex ratio for childhood cancer in India has a bias towards boys at the level of diagnosis, which is more pronounced in northern India and in situations demanding greater financial commitment. Addressing societal sex bias and enhancing affordable health care for girls should be pursued simultaneously in India.Funding: None.Translation: For the Hindi translation of the abstract see Supplementary Materials section. [ABSTRACT FROM AUTHOR]

Background: Allogeneic hematopoietic stem cell transplantation activity is growing globally as one of the curative treatment options for many hematological diseases. A stem cell transplant registry plays an important role in such treatment. Setting up a functional stem cell donor registry is quite challenging with several issues such as resources, donor recruitment, donor attrition, ethnicity, lack of support, and impact of coronavirus disease 2019 (COVID-19). Aim: The aim of the current study was to present the experience of a resource-constrained registry in India as well as the effect of COVID-19 on its operations. Settings and Design: The present study was a descriptive study which was designed to study the functioning of a resource-constrained registry from north India. Materials and Methods: The study data for the period of 2012--2020 pertaining to donor recruitment, number of searches, number of matched donors, number of transplants performed, and donor attrition was collected from the registry software "Prometheus." Statistical Analysis: Descriptive statistics such as frequency and percentage was used. Results: During the past 9 years of operation, the registry has faced several issues pertaining to lack of funds, donor recruitment, donor attrition, and COVID-19 has exacerbated their pain points significantly. The registry has recruited a total of 20,093 donors, of which only 7794 have been human leukocyte antigen typed, with the remaining samples awaiting funding. Out of this small number of typed donors, registry has performed 15 matched unrelated donor transplants for Indian and international patients. As a result of COVID-19, donor attrition was on the rise and showed a peak in 2020. During the year 2020, the number of searches, donor recruitment camps, and donors all decreased considerably. Conclusion: The establishment and operation of a stem cell transplant registry necessitate extensive planning and resources. The resource-constrained registries face a number of issues pertaining to effective functioning and future developments. The external support and awareness for the cause can help minimize the pain points of these registries. [ABSTRACT FROM AUTHOR]

Objective: The present study aims to provide outcome data in children with relapsed acute lymphoblastic leukemia (ALL) over two decades and variables that impact survival., Method: This retrospective study included children who were diagnosed with ALL and treated at our center and relapsed between March 2002 and March 2021., Results: A total of 100 children (64 boys, 36 girls) were included; 80 had B-ALL, 20 had T-ALL. 50 children had a very early relapse, while 25 each had an early and late relapse. The site of relapse was bone marrow in 57, isolated central nervous system (CNS) in 10, isolated testicular in 1, and combined bone marrow and CNS relapse in 32 children. Thirty-six families opted for the best supportive care; 23 of these had very early relapse. Among the 35 who were in remission following induction chemotherapy, 32 (91%) underwent hematopoietic stem cell transplantation (HSCT); 17/32 (53%) were alive and disease-free. Overall survival (OS) was 19 (19%) with a median follow-up of 23.5 months with a significantly improved survival post-measurable risk of disease (MRD) based risk stratification (4% vs 35%, P = 0.02). The OS with very early, early, and late relapses were 8%, 28%, and 32% (P = 0.018), and 15%, 12.5%, and 50% with bone marrow, combined and isolated CNS relapses (P = 0.008)., Conclusion: Relapsed ALL remains a challenge, with OS of 19% and 53% among those who underwent HSCT. Abandonment after relapse continues to be prevalent, and we need to integrate social support for providing care and optimal treatment.

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., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background Lower-middle-income countries face unique problems in the management of pediatric acute myeloid leukemia (AML) due to which the outcomes have not kept pace with developed nations. In India, data on childhood AML is sparsely available, thus making a true assessment of disease trends difficult. The current systematic review was undertaken to assess the outcomes of childhood AML from published literature from India over a period of 10 years (2011–2021). Materials and Methods A systematic search of MEDLINE, Google Scholar, and SCOPUS was performed as per preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement from January 1, 2011 to December 31, 2021. In addition, International Society of Pediatric Oncology (SIOP) conference abstracts were also screened for relevant studies on AML from India. This study was registered in PROSPERO (ID42021273218). Results A total of 1,210 patients from 19 studies were included. Standard 3 + 7 and MRC AML based regimens were commonly adopted regimens for induction. Remission rates varied between 56 and 95%. Overall treatment-related mortality across studies was 23.2% (95% confidence interval [CI]: 10.3–35.9%). The mean incidence of treatment abandonment was 19.3% (95% CI: 10.9–27.5%). Event-free survival and overall survival were in the range of 28 to 55% and 15 to 66%, respectively. Hematopoietic stem cell transplantation was performed only on a small subset of patients. Conclusion Outcomes of pediatric AML in India continue to be suboptimal with high treatment abandonment and toxic deaths. Ensuring uniform access to therapy and supportive care along with a robust social support system would improve outcomes of childhood AML in India. [ABSTRACT FROM AUTHOR]

Introduction: Respiratory syncytial virus (RSV) is a common cause of morbidity among hematopoietic stem cell transplant (HSCT) recipients, with RSV-associated lower respiratory tract infection carrying high mortality rates. There have been no large studies till date, describing the incidence, clinical features, and outcomes of RSV infection among adult HSCT recipients in India. Methods: A prospective cohort of 100 adults who underwent HSCT was followed up for a maximum period of 18 months starting from the date of transplantation for any episode of respiratory tract infectious disease (RTID). Respiratory samples were collected for laboratory confirmation of the presence and subtyping of RSV by real-time reverse transcriptase-polymerase chain reaction. Results: The study population comprised of 66% (66/100) males and 34% (34/100) females. Autologous HSCT recipients constituted 78% (78/100) and allogeneic HSCT recipients constituted 22% (22/100) of the study population. The incidence of RSV-RTID among adults after HSCT was 0.82/100 patient months. Most cases occurred during the winter season and the predominant subtype was RSV-A (9/11, 81.8%). Lower RTID was the most common clinical diagnosis made at presentation (9/11, 81.8%). Female gender was predictive of RSV-RTID (log rank P = 0.002). All the RSV-RTID episodes recovered completely without targeted therapy. Conclusion: RSV is a significant cause of morbidity among adult HSCT recipients in India. Prophylaxis and treatment measures need to be instituted after a proper risk-benefit assessment. Longitudinal studies with larger sample sizes are needed to confirm these results. [ABSTRACT FROM AUTHOR]

Background: The present study reports myeloablative total body irradiation (TBI) on an isocentrically mounted linac by laying the patient on the floor and management of abutting radiation fields and partial shielding of lungs. Dosimetrical efficacy of this novel technique was evaluated. Materials and methods: In this retrospective study, dosimetrical parameters from TBI plans on whole-body CT scans of 46 patients were analysed. The prescribed dose to TBI was 12 Gy in six fractions delivered over a period of 3 days for myeloablative conditioning. TrueBeam STx platform Linac (Varian Medical Systems Inc., Palo Alto, CA, USA) was used to deliver opposing fields. Radiation fields were abutted to form a single large field using an arithmetic formula at source-to-skin-distance of 210 cm. Results: Discrepancies in dose calculated by treatment planning system were within 1·6% accuracy, and dose profile at the junction of abutting radiation fields was reproduced within 3·0% accuracy. The real treatment time for each patient was ~30 minutes/fraction. Monitor unit was weighted for multiple sub-fields to achieve dose homogeneity within 5·0% throughout the whole body, and the mean dose to lung was ≤10 Gy. Conclusion: Our abutting radiation field technique for myeloablative TBI is feasible in any existing linac bunker. 'Island-blocking' is feasible in this technique using multi-leaf collimator. This technique is cost-effective as it does not require any costly equipment than the readily available equipment in any radiotherapy facility. In general, TBI requires laborious planning procedures and spacious linac bunkers; this novel technique has the potential to change previously held notions. [ABSTRACT FROM AUTHOR]

Justification: In India, there is a lack of uniformity of treatment strategies for aplastic anemia (AA), and many children are managed only with supportive care due to non-availability of hematopoietic stem cell transplantation (HSCT). Process: Eminent national faculty members were invited to participate in the process of forming a consensus statement in Hyderabad in July, 2016. Draft guidelines were circulated to all members, and comments received in a online meeting in October, 2020 were incorporated into the final draft. These were approved by all experts. Objective: To facilitate appropriate management of children with acquired aplastic anemia. Recommendations: Key recommendations are: i) A bone marrow biopsy is must to make a diagnosis of AA; ii) Rule out inherited bone marrow failure syndromes (IBMFS), connective tissue disorders, viral infections, paroxysmal nocturnal hemoglobinuria (PNH), drug or heavy metal induced marrow suppression in all cases of AA; iii) Conservative approach to transfusions should be followed, with a target to keep hemoglobin >6 g/dL in children with no co-morbidities; iv) HLA-matched sibling donor HSCT is the preferred choice of treatment for newly diagnosed very severe/severe AA; v) In absence of HLA-matched family donor, a matched unrelated donor (MUD) transplant or immunosuppressive therapy (IST) should be considered as alternate choice based on physician expertise; vi) Fludarabine, cyclophosphamide and anti-thymocyte globulin (ATG) based conditioning with cyclosporine and methotrexate as graft versus host disease (GvHD) prophylaxis is the preferred regimen; vii) Horse ATG and cyclosporine are the recommended drugs for IST. One should wait for 3–6 months for the response assessment and consideration of next line therapy. [ABSTRACT FROM AUTHOR]

X-linked agammaglobulinemia (XLA) is an X-linked recessive primary immunodeficiency disorder caused due to a pathogenic variant in the Bruton tyrosine (BTK) gene with an incidence of 1:379,000 live births and 1:190,000 male births. Patients affected with XLA present with recurrent infections of the gastrointestinal and respiratory tracts. Here we report the first case series of 17 XLA patients of 10 South Indian families with a wide spectrum of clinical and genetic features. In our cohort, patients presented mainly with recurrent pneumonia, gastrointestinal infection, otitis media, pyoderma, abscesses, empyema, arthritis, and osteomyelitis. Using next-generation and Sanger sequencing we have identified 10 unique pathogenic and likely pathogenic variants in 17 patients. This encompasses three nonsynonymous, two stop-gain, two frameshifts, two structural, and one splicing variant, out of which two of them are novel. Based on the type of variant, patients had variable clinical features and treatment responses. We have also evaluated Btk protein expression for six patients in comparison to the healthy individuals and determined mosaic Btk expression patterns in four mothers. We have also performed family screening in 6 families using Sanger sequencing and identified 19 carriers for the variant. The diagnosis for the patients led to the proper treatment i.e. 15 patients were on intravenous immunoglobulin (IVIG) and the other two had successful hematopoietic stem cell transplantation (HSCT). Unfortunately, two of our patients died due to sepsis, while on IVIG. We envision the present study could help in better understanding of patients with XLA and help in family screening and prenatal diagnosis. To the best of our knowledge, this is the largest case series of patients affected with XLA from South India. [ABSTRACT FROM AUTHOR]

Background: The coronavirus disease 2019 (COVID‐19) pandemic led the Indian government to announce a nationwide lockdown on March 23, 2020. This study aimed to explore the impact of the pandemic on the accessibility of care for children with cancer and to view strategies adopted by hospitals for service delivery. Methods: Weekly average of childhood cancer (≤18 years) patient registrations during pre‐lockdown period (January 1 to March 23, 2020) were compared with post‐lockdown period (March 24 to May 31, 2020). The effect on the scheduled treatment was investigated for post‐lockdown period. A survey of health care providers was conducted to determine centers' adopted strategies. Results: In 30 participating centers, 1146 patients with childhood cancer (797 pre‐lockdown period and 349 post‐lockdown period) were registered. The weekly average registration was 67.3 and 35.5 patients during pre‐lockdown and post‐lockdown respectively (decline of 47.9%). Although most centers experienced this decline, there were 4 that saw an increase in patient registrations. The distribution of patients registered post‐lockdown was found significantly different by age (lesser older age, P =.010) and distance (lesser travel distance, P =.001). 36.1% of patients, who were scheduled for any of the treatment modalities (chemotherapy, surgery, radiotherapy, and hematopoietic stem cell transplantation) during the post‐lockdown period, experienced delays. Centers adopted several strategies including modifications to treatment protocols, increased use of growth factors, and increased support from social organizations. Conclusions: This multicenter study from India suggests that the COVID‐19 pandemic and the lockdown impacted 2 out of 3 children with cancer. The effect of this on survival is yet to be established. The coronavirus disease 2019 pandemic and the national lockdown in India since March 2020 led to delays in diagnosis and interruptions in the treatment of childhood cancer. This study reports a decline of 47.3% in the weekly average patient registration between pre‐lockdown and post‐lockdown, and 36.1% of patients experienced delays in 1 or more treatment modalities during the post‐lockdown period. [ABSTRACT FROM AUTHOR]

BACKGROUND: Plerixafor is used for patients at risk of Stem cell mobilization failure based on clinical factors or low peripheral blood CD34 count. It is also added upfront to any mobilization irrespective of risk factor, but the cost-effectiveness of the approach is an issue. Data on plerixafor in different settings of autologous hematopoietic stem cell (HSC) collection from India are scant. We are hereby reporting the experience of failure/success of mobilization rate and few important significant variables (CD34+ dosage, failed collection) between plerixafor and granulocyte colony-stimulating factor alone groups among autologous hematopoietic stem cell transplantation (aHSCT) at our institute. METHODS: This was a record-based single-center study on patients who underwent aHSCT from January 2013 to June 2019 at a tertiary care hospital. Descriptive statistics were used for baseline characteristics, transplant-related factors, and peritransplant outcomes. All statistical analyses were performed at the 5% significance level. RESULTS: During the study duration, a total of 96 patients had undergone autologous hematopoietic stem cell collection (aHSCC), all by peripheral blood stem cell harvest, requiring 131 apheretic collections. Of the total 131 collections in 96 patients, plerixafor was used in 63 apheresis collections (48% of total pheresis) in 40 patients. Among the 40 patients who were administered plerixafor to augment the collection, 34 patients had upfront use of plerixafor. We did not observe any significant adverse event related to plerixafor use. CONCLUSION: A rational utilization of plerixafor can facilitate the process and logistics of aHSCC outcome. [ABSTRACT FROM AUTHOR]

Background: Timeline is a key factor for hematopoietic stem cell transplant (HSCT) recipient. HSCT by matched unrelated donor (MUD) is a standard definitive therapeutic approach for many hematological disorders which are not amenable to chemotherapy and other conventional treatment. Aims and Objectives: The aim of the present study was to compare the turnaround time (TAT) involved in completion of MUD HSCT workup from an Indian registry (Genebandhu) with international registries. Materials and Methods: On receipt of pre-transplant matching request through a transplant physician, patient's human leukocyte antigen (HLA) type was entered in both Genebandhu and World Marrow Donor Association search tool for initiating a "search." The software gave the descending order of the best possible matches by performing computational analysis. The search result was considered a "match" when potential 10/10 HLA match was found. The average TAT was calculated in the middle of search request and HLA confirmatory typing (CT) and infectious disease marker (IDM). Further, TAT was also determined between the infusion of harvested stem cell product and CT and IDM. At last, the total time engaged in completion of each MUD HSCT workup was determined and compared in national versus international registries. Results: The average TAT involved in between search request and CT and IDM was 71 days in case of global registry and 67 days in case of Genebandhu. Similarly, the average TAT involved between infusion of harvested cell product and CT and IDM testing in case of donor identified in global stem cell registry was 65 days whereas 45 days in case of Genebandhu. At last, the average time associated with the finishing of a MUD workup was 136 days in case of global registry, whereas 112 days in the case of Genebandhu at P ≤ 0.05 with a 95% confidence interval. Conclusion: To conclude, the average TAT obtained through this study clearly demonstrates the advantages in terms of donor availability for MUD HSCT through the national registry. [ABSTRACT FROM AUTHOR]

Beta-thalassemia major is characterized by a genetic deficiency in synthesis of beta-globin chains, resulting in reduced levels of functional hemoglobin. It is characterized by anemia, hepatosplenomegaly, and iron overload due to repeated blood transfusion. Hematopoietic stem cell transplantation is currently the only known curative treatment. We present a case of a 10-year-old girl with beta-thalassemia major who was successfully cured with allogeneic booster umbilical cord blood (UCB) transplantation with outcome data after 3 years of transplantation, in India. Postdiagnosis, she was on regular once-a-month blood transfusion until the age of 10 years, with no improvement. No serious adverse events occurred in the patient post-UCB transplantation. Chronic graft versus host disease was limited and was managed by medicines. Signs of primary graft rejection were also not seen. [ABSTRACT FROM AUTHOR]

BACKGROUND: Mononuclear cells (MNCs) are considered equivalent to hematopoietic stem cells, and differential count using peripheral smear was routinely practiced to enumerate MNC. Flow cytometry plots used for CD34 enumeration assay can also be used in MNC enumeration as it counts more WBC events than manual methods. The aim was to determine the relationship and degree of agreement between peripheral smear and flow cytometry in MNC enumeration of peripheral blood stem cell (PBSC) products. METHODS: In 63 patients, 73 PBSC products were collected between January 2017 and September 2019. The differences in MNC count estimated by peripheral smear method and from flow cytometry plots used for CD34 enumeration were analyzed using Mann--Whitney test. Agreement between the two methods for MNC enumeration was determined by regression analysis. Receiver operating characteristic curve was performed to determine MNC threshold in peripheral blood and PBSC product for adequate mobilization and harvest. RESULTS: There was no difference in enumeration of median MNC count between peripheral smear and flow cytometry (52% vs. 59%, P = 0.185) in PBSC product. However, regression analysis indicated a constant and proportional difference between the methods with r = 0.52. Cumulative sum test for linearity showed deviation from linearity (P = 0.04). MNC counts in peripheral blood failed to achieve discrimination capacity in predicting adequate CD34+ yield/kg body weight in product. CONCLUSION: Peripheral smear estimated lower MNC counts than flow cytometry with weaker agreements between the two methods. Hence, MNC count derived from flow cytometry plot can substitute peripheral smear method for MNC dose calculations. MNC dose at 3.4 x 108/kg consistently predicted >2 x 106/kg CD34+ cells collected. [ABSTRACT FROM AUTHOR]

There is paucity of data on outcomes of MSD‐HSCT in children with relapsed or high‐risk AML from developing countries, which have unique challenges including adverse host factors and resource constraints. We retrospectively reviewed records of children (age ≤ 18 years) who underwent MSD‐HSCT for AML at our center from 2009 to 2019 to evaluate clinical outcome and its predictors using Cox proportional hazards model. There were 46 children (36 boys and 10 girls) with mean age 10.7 ± 4.8 years. Indication for HSCT was relapsed AML in CR2 (n = 37), primary refractory (n = 3), or relapsed refractory disease (n = 3); high‐risk (n = 1) or secondary (n = 2) AML in CR1. Five‐year EFS and OS were 33.3 ± 7.2% and 36.3 ± 7.6%, respectively. On multivariate analysis, CR1 duration less than 12 months, presence of active disease at transplant, and use of bone marrow stem cell graft were associated with poorer EFS and OS. There was one (2.2%) TRM, while disease relapse occurred in 20/40 patients who underwent HSCT in remission. Though the 5‐year EFS and OS were inferior to results reported from high‐income countries, relapse (and not TRM) was the major cause of treatment failure. A well‐sustained CR1, achievement of disease remission, and use of peripheral blood allograft seem imperative to a successful transplant. Targeted therapy along with HSCT may be the option for those with early relapse. [ABSTRACT FROM AUTHOR]

Background: Wiskott Aldrich syndrome (WAS) is characterized by bleeding manifestations, recurrent infections, eczema, autoimmunity, and malignancy. Over the last decade, improved awareness and better in-house diagnostic facilities at several centers in India has resulted in increased recognition of WAS. This study reports collated data across major primary immunodeficiency diseases (PID) centers in India that are involved in care of children with WAS and highlights the varied clinical presentations, genetic profile, and outcomes of patients in India. Methods: Request to share data was sent to multiple centers in India that are involved in care and management of patients with PID. Six centers provided requisite data that were compiled and analyzed. Results: In this multi-institutional cohort, clinical details of 108 patients who had a provisional diagnosis of WAS were received. Of these, 95 patients with 'definite WAS' were included Fourteen patients were classified as XLT and 81 patients as WAS. Median age at onset of symptoms of patients was 3 months (IQR 1.6, 6.0 months) and median age at diagnosis was 12 months (IQR 6,48 months). Clinical profile included bleeding episodes (92.6%), infections (84.2%), eczema (78.9%), various autoimmune manifestations (40%), and malignancy (2.1%). DNA analysis revealed 47 variants in 67 cases. Nonsense and missense variants were the most common (28.4% each), followed by small deletions (19.4%), and splice site defects (16.4%). We also report 24 novel variants, most of these being frameshift and nonsense mutations resulting in premature termination of protein synthesis. Prophylactic intravenous immunoglobulin (IVIg) was initiated in 52 patients (54.7%). Hematopoietic stem cell transplantation (HSCT) was carried out in 25 patients (26.3%). Of those transplanted, disease-free survival was seen in 15 patients (60%). Transplant related mortality was 36%. Outcome details were available for 89 patients. Of these, 37% had died till the time of this analysis. Median duration of follow-up was 36 months (range 2 weeks- 12 years; IQR 16.2 months- 70 months). Conclusions: We report the first nationwide cohort of patients with WAS from India. Bleeding episodes and infections are common manifestations. Mortality continues to be high as curative therapy is not accessible to most of our patients. [ABSTRACT FROM AUTHOR]

Introduction X-linked adrenoleukodystrophy (X-ALD) is a devastating disease with a wide spectrum of presentation ranging from asymptomatic to a rapidly progressive childhood cerebral form. The gene responsible for adrenoleukodystrophy is ABCD1 gene, required for β oxidation of fatty acids in various tissues. While biochemical and molecular techniques are available to confirm the diagnosis, brain magnetic resonance imaging (MRI) utilizing Loes score has been used for both prognosis and timely direction of hematopoietic stem cell therapy. Materials and Methods During the study period of 2016 to 2020, 22 individuals including 19 individuals with features suggestive of X-ALD and 3 asymptomatic siblings were evaluated from a single center in North India. After biochemical and molecular confirmation of the disease, detailed clinical and radiological findings using MRI brain were documented. A radiological scoring pattern proposed by Loes was employed to identify the severity of the disorder. Results The most common clinical presentations were visual difficulty and muscular weakness (58%). All symptomatic individuals had classic neuroimaging findings in the form of hyperintensities involving the parieto-occipital area and splenium of corpus callosum. Severe involvement in the form of global atrophy was observed in 52.6% of individuals. Asymptomatic siblings also showed neurological involvement based on MRI with highest Loes score of 9 in one individual. Conclusion This case series describes the clinical and radiological profile and employment of Loes score in individuals with X-ALD. Early identification of asymptomatic individuals by neuroimaging and use of Loes severity score for monitoring and disease progression will help in making therapeutic decisions in a timely manner. [ABSTRACT FROM AUTHOR]

Introduction: Gaucher disease (GD) is a rare autosomal recessive lysosomal storage disorder, in which biallelic pathogenic variants in the Glucosidase beta acid (GBA) gene result in defective functioning of glucosylceramidase that causes deposition of glucocerebroside in cells. GD has 3 major types namely, non-neuronopathic (type I), acute neuronopathic (type II), and chronic neuronopathic (type III). Definite treatment options are limited and expensive. They succumb early to the disease, if untreated. There is paucity of studies from the Indian subcontinent, which elicit the factors resulting in their premature mortality. Materials and Methods: A retrospective study was carried out in a tertiary care setting of South India to assess the clinical profile, mutation spectrum, and various management strategies (only supportive therapy, enzyme replacement therapy [ERT], substrate reduction therapy [SRT] haematopoietic stem cell transplant [HSCT]), and mortality predictors of patients with GD from 2004 to 2019. A Kaplan-Meier survival curve was plotted. In silico predictions were performed for novel variants. Results: There were 60 patients with all types of GD seen over the study period of 15 years. Their median age at diagnosis was 2 years. The median follow-up was for 5 years (interquartile range [IQR] = 2–8). The overall mortality rate was 35%; however, it was only 10% in those receiving definite treatment. Mortality was higher (47.5%) by more than 4 folds in those only on supportive therapy. The median survival from the time of diagnosis was 6.3 years (IQR = 3.5–10.8) in the definite treatment group and 3.5 years (IQR = 1–5) in those on supportive therapy. The Kaplan-Meier survival analysis showed significant (p value 0.001) mortality difference between these groups. The multiple logistic regression analysis found the neuronopathic type (OR = 5) and only supportive therapy (OR = 6.3) to be the independent risk factors for premature mortality. Conclusion: GD is a rare disease with a high mortality rate, if left untreated. ERT and SRT are the definitive treatments which increase the survival. In resource-limited settings like India, with higher prevalence of the neuronopathic type, HSCT may be a more suitable definitive treatment option, due to its one-time intervention and cost, assuming similar efficacy to ERT. However, the efficacy and safety of HSCT in GD needs to be established further by substantial patient numbers undergoing it. [ABSTRACT FROM AUTHOR]

Background: Primary immunodeficiency disorders are genetically heterogeneous immune disorders with a wide range of infectious and non-infectious manifestations. Objective: To describe a single-center experience of primary immunodeficiency disorders. Design: Retrospective analysis from January 2015 to January 2020. Setting: Tertiary care children's hospital. Participants: One hundred and twelve children (<18 years) diagnosed with primary immunodeficiency disorders. Outcome measure: Diagnostic spectrum, clinical features, and outcome. Results: The median (IQR) age of the first clinical manifestation and lag time in diagnosis was 10 (27) and 11 (18) months, respectively. Twenty-seven children (24%) were diagnosed during their first presentation. Thirty-six (32%) children had phagocytic disorders, 20 (17.8%) had combined/cellular defects, 18 (16%) had predominant antibody deficiencies and 17 (15%) had disorders of immune dysregulation. Non-infectious manifestations were seen in 54 (48%). Eight children underwent hematopoietic stem cell transplantation, 44 (39%) children were on antimicrobial prophylaxis and supportive therapy, 36 (32%) were lost to follow-up and 24 (21%) children died. Conclusion: Congenital defects of phagocyte function, followed by combined/cellular defects are the commonest primary immune deficiencies (PIDs) identified in southern India. Long lag time in diagnosis and high mortality in our cohort emphasizes the need for early diagnosis and early referral. [ABSTRACT FROM AUTHOR]

Background: Chronic granulomatous disease (CGD) is an inherited defect in phagocytic respiratory burst that results in severe and life-threatening infections in affected children. Single center studies from India have shown that proportion of autosomal recessive (AR) CGD is more than that reported from the West. Further, affected patients have high mortality rates due to late referrals and difficulties in accessing appropriate treatment. However, there is lack of multicentric collaborative data on CGD from India. Objective: To describe infection patterns, immunological, and molecular features of CGD from multiple centers in India. Methods: A detailed proforma that included clinical and laboratory details was prepared and sent to multiple centers in India that are involved in the care and management of patients with inborn errors of immunity. Twelve centers have provided data which were later pooled together and analyzed. Results: Of the 236 patients analyzed in our study, X-linked and AR-CGD was seen in 77 and 97, respectively. Male female ratio was 172:64. Median age at onset of symptoms and diagnosis was 8 and 24 months, respectively. Common infections documented include pneumonia (71.6%), lymphadenitis (31.6%), skin and subcutaneous abscess (23.7%), blood-stream infection (13.6%), osteomyelitis (8.6%), liver abscess (7.2%), lung abscess (2.9%), meningoencephalitis (2.5%), splenic abscess (1.7%), and brain abscess (0.9%). Forty-four patients (18.6%) had evidence of mycobacterial infection. Results of molecular assay were available for 141 patients (59.7%)— CYBB (44.7%) gene defect was most common, followed by NCF1 (31.9%), NCF2 (14.9%), and CYBA (8.5%). While CYBA variants were documented only in Southern and Western parts of India, a common dinucleotide deletion in NCF2 (c.835_836delAC) was noted only in North Indian population. Of the 174 patients with available outcome data, 67 (38.5%) had expired. Hematopoietic stem cell transplantation was carried out in 23 patients, and 12 are doing well on follow-up. Conclusions: In India, proportion of patients with AR-CGD is higher as compared to Western cohorts, though regional differences in types of AR-CGD exist. Clinical profile and mortality rates are similar in both X-linked and AR-CGD. However, this may be a reflection of the fact that milder forms of AR-CGD are probably being missed. [ABSTRACT FROM AUTHOR]

Background: Severe Combined Immune Deficiency (SCID) is an inherited defect in lymphocyte development and function that results in life-threatening opportunistic infections in early infancy. Data on SCID from developing countries are scarce. Objective: To describe clinical and laboratory features of SCID diagnosed at immunology centers across India. Methods: A detailed case proforma in an Excel format was prepared by one of the authors (PV) and was sent to centers in India that care for patients with primary immunodeficiency diseases. We collated clinical, laboratory, and molecular details of patients with clinical profile suggestive of SCID and their outcomes. Twelve (12) centers provided necessary details which were then compiled and analyzed. Diagnosis of SCID/combined immune deficiency (CID) was based on 2018 European Society for Immunodeficiencies working definition for SCID. Results: We obtained data on 277 children; 254 were categorized as SCID and 23 as CID. Male-female ratio was 196:81. Median (inter-quartile range) age of onset of clinical symptoms and diagnosis was 2.5 months (1, 5) and 5 months (3.5, 8), respectively. Molecular diagnosis was obtained in 162 patients - IL2RG (36), RAG1 (26), ADA (19), RAG2 (17), JAK3 (15), DCLRE1C (13), IL7RA (9), PNP (3), RFXAP (3), CIITA (2), RFXANK (2), NHEJ1 (2), CD3E (2), CD3D (2), RFX5 (2), ZAP70 (2), STK4 (1), CORO1A (1), STIM1 (1), PRKDC (1), AK2 (1), DOCK2 (1), and SP100 (1). Only 23 children (8.3%) received hematopoietic stem cell transplantation (HSCT). Of these, 11 are doing well post-HSCT. Mortality was recorded in 210 children (75.8%). Conclusion: We document an exponential rise in number of cases diagnosed to have SCID over the last 10 years, probably as a result of increasing awareness and improvement in diagnostic facilities at various centers in India. We suspect that these numbers are just the tip of the iceberg. Majority of patients with SCID in India are probably not being recognized and diagnosed at present. Newborn screening for SCID is the need of the hour. Easy access to pediatric HSCT services would ensure that these patients are offered HSCT at an early age. [ABSTRACT FROM AUTHOR]

Background: Hematopoietic stem cell transplantation (HSCT) is the curative option for many primary immune deficiency disorders (PID). In the last 5 years, increased awareness, availability of diagnostics based on flow cytometry, genetic testing, improved supportive care, use of reduced toxicity conditioning, and success of haploidentical donor HSCT have improved access to HSCT for children with PID in India. We present results on children with PID who underwent HSCT across India and the factors that influenced outcome. Patients and Methods: We collected retrospective data on the outcome of HSCT for PID from seven centers. We analyzed the impact of the type of PID, conditioning regimen, time period of HSCT- before or after January 2016, graft versus host disease prophylaxis, cause of mortality and overall survival. Results: A total of 228 children underwent HSCT for PID at a median age of 12 months (range, 1 to 220 months) with a median follow up of 14.4 months. Infants accounted for 51.3% of the cohort and the male female ratio was 3:1. SCID (25%) and HLH (25%) were the more frequent diagnoses. Matched family donor was available in 36.4% and 44.3% children had a haploidentical HSCT. Reduced and myeloablative conditioning regimens were used with 64% children receiving a treosulfan based conditioning regimen. Peripheral blood stem cells were the predominant graft source at 69.3%. The survival in infants (60.2%) was inferior to children aged over 1 year (75.7% p value = 0.01). Children with Wiskott Aldrich syndrome (74.3%) and chronic granulomatous disease (82.6%) had the best outcomes. The survival was superior in children receiving HSCT from a matched sibling (78%) versus an alternate donor HSCT (61% p value = 0.04). In the cohort transplanted after January 2016 survival improved from 26.8% to 77.5% (p value = 0.00). Infection remains the main cause of mortality at in over 50% children. The 5-year overall survival rate was 68%. Conclusion: Survival of children with PID undergoing HSCT in India has improved dramatically in last 5 years. Alternate donor HSCT is now feasible and has made a therapeutic option accessible to all children with PID. [ABSTRACT FROM AUTHOR]

Hematopoietic stem-cell transplantation (HSCT) is a life-saving procedure often performed to cure relapsed and difficult-to-treat malignancies. Only a handful of centers in India were initially involved in the delivery of these services. However, in the last decade, more than 100 centers in the private and public domain have started offering transplant services in the country. Moreover, there are funding options, which has opened up this expensive treatment options for economically backward patients. Costs apart, there are multiple social, familial, and emotional challenges faced by these patients. A multidisciplinary support team involving social workers, psychologists, and transplant nurses, besides the treating hematologist/oncologist, is required for the optimum care of these patients. These challenges, in the Indian context, are often unique. Unfortunately, there is limited information and resource available to guide counseling of patients planned for HSCT in India. We conducted a workshop at our center where a panel of experts with experience in dealing with patients undergoing HSCT discussed issues faced by them. These discussions constitute a valuable resource for counseling patients planned for HSCT. They were transcribed by a postgraduate doctor and are summarised here in a case-based format. [ABSTRACT FROM AUTHOR]

Purpose: Hematopoietic stem cell transplant (HSCT) is an intense form of treatment, resulting in major symptom burden but can prove curative. The quality of life (QOL) is a major endpoint for these patients as the survival rate in them has improved over time. The aim of the study is to assess the QOL and symptom burden of hematological malignancy patients at admission to hospital for HSCT, at 1 month and at 3 months following HSCT., Methods: This prospective observational study was done on hematological malignancy patients who were admitted for HSCT in a regional cancer center. The study subjects were assessed by the Functional Assessment of Cancer Therapy-Bone Marrow Transplant Scale (FACT-BMT Scale), Edmonton Symptom Assessment Scale-revised (r-ESAS), and Depression, Anxiety and Stress Scale-21 Items (DASS-21) at the time of hospital admission for transplantation, on day 30 (~ 1 month) and day100 (~ 3 months) of transplantation., Results: A total of 68 patients were included in this study. FACT-BMT scores have decreased from baseline (F0) to the first follow-up (F1) and then increased in the third follow-up (F2). The maximum r-ESAS mean score was for tiredness among all other symptoms at F0 as well as at F1 and at F2. The DASS 21 scores for depression, anxiety, and stress were maximum during F1 and minimum during F2., Conclusion: Symptom burden is maximum during the first month of BMT, which improves later and QOL becomes improved with time., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

• Haploidentical stem cell transplantation with post-transplant cyclophosphamide can be considered a viable option in children with Fanconi anemia, particularly in resource-limited settings given the high costs of hematopoietic stem cell transplantations, with an overall survival of 68.4%. • Peripheral blood stem cells provide early engraftment, decreasing the risk of prolonged neutropenia and sepsis, with a focus on maintaining CD34 and CD3 dose of a minimum of 5 × 106/kg and 1.5 × 108/kg recipient body weight, respectively, in the infused graft. • Supportive care measures, including N -acetyl cysteine infused concomitantly with cyclophosphamide on day +3 and day +4, can help decrease the incidence of severe mucositis and transaminitis and thereby reduce regimen-related toxicity. • Monitoring ferritin as a surrogate marker for IL-6 levels and cytokine release syndrome with log increases combined with clinical features as the basis for instituting early steroids can decrease the mortality associated with cytokine release syndrome. • Ruxolitinib can be a useful second-line agent for chronic graft-versus-host disease (GVHD) with good responses in those with skin and mouth GVHD. Fanconi anemia is the most common inherited bone marrow failure syndrome, and hematopoietic stem cell transplantation (HSCT) is the only curative option. Post-transplant cyclophosphamide (PTCy) is challenging in this group of children, given their increased sensitivity to chemotherapy. We performed a retrospective analysis of the data on children diagnosed with Fanconi anemia who underwent a haploidentical HSCT with PTCy from January 2014 to December 2019. Nineteen children (male/female, 0.75:1) underwent 21 haplo-HSCTs with PTCy. Fludarabine, low-dose cyclophosphamide, and 200 centi-gray total body irradiation were included in the conditioning regimen with 25 mg/kg PTCy on days +3 and +4. Haplo-graft was from a sibling in 38% and father in 57% of transplants. The source of stem cells was peripheral blood stem cells in 81% and bone marrow in 19% of transplants, with a median CD34 dose of 5.0 × 106/kg. We documented engraftment in 84% and primary graft failure in 10% of transplants. N -acetylcysteine (NAC) was infused concomitantly during cyclophosphamide in 13 children. Grade 2 and 3 mucositis was lower among those who received NAC as compared to those who did not (30% and 15% versus 33% and 50%), while transaminitis was higher among those who did not receive the infusion. The incidence of acute graft-versus-host disease (GVHD) was 68%, and 81% of these were steroid responsive (grade I/II). We documented chronic GVHD in 25% children, predominantly involving the skin and mouth, which responded to low-dose steroids and ruxolitinib. Serum ferritin was monitored twice weekly as a surrogate marker for cytokine release syndrome due to nonavailability of IL-6 levels. A 1- or 2-log increase in the titers of ferritin associated with clinical features guided the early addition of steroids in the periengraftment period. The mean survival was found to be less among those with high serum ferritin (>10,000 ng/dL) in the periengraftment period as compared to those with ferritin <10,000 ng/dL (mean survival of 25 ± 10 months versus 50 ± 6 months, respectively). The overall survival in our cohort was 68.4%, with a mean survival time of 41.5 months (95% confidence interval, 29.3 to 53.8 months), with a statistically significant correlation between inferior outcome and having received over 15 transfusions before HSCT (P =.01). PTCy can be considered a viable option in children with Fanconi anemia, particularly in resource-limited settings given the high costs of HSCTs. Focused interventions in this subset of children help improve survival outcomes. Early identification of cytokine release syndrome and risk-adapted steroid therapy during engraftment helps prevent mortality. The concomitant use of NAC during cyclophosphamide infusion helps reduce oxygen free radical related tissue damage and regimen-related toxicity. [ABSTRACT FROM AUTHOR]

Background: Infection and relapse constitute the two main challenges in the management of acute myeloid leukemia (AML) in children. Real-world data in children treated in low-and-middle income countries are sparse as the cost of supportive care is high. Patients and Methods: We present data on children up to 18 years of age undergoing chemotherapy for AML as per UKMRC AML protocol from 2002 to June 2019 and pattern of sepsis. Results: The incidence of culture-positive sepsis was similar pre- and post-2012 (52.6% vs. 72.4%), Klebsiella pneumoniae being the most common organism. There was a significant increase in carbapenem resistance post 2012 (14% vs. 67%, P = 0.032). Sepsis-related induction mortality has remained at 6.2% despite an increase in drug-resistant bacterial infections over two decades. The overall survival was 53% (n=48), with a plateau in the survival curve after 24 months, relapse being the most common cause of death (69%). Conclusions: Sepsis-related induction mortality can be maintained at less than 10% in children undergoing chemotherapy for AML, despite increasing drug-resistant bacteremia, with adequate supportive care and trained personnel including pediatric intensivists and nurses. [ABSTRACT FROM AUTHOR]

• With advances in supportive care and a higher index of suspicion for adverse effects, early interventions can help provide equivalent overall survival rates of 93% in children undergoing family and alternative donor hematopoietic stem cell transplantation (HSCT) for thalassemia major. • Immediate complications like infections (25% versus 21%) are similar, but the incidence of posterior reversible encephalopathy syndrome is higher (10% versus 3%) in matched unrelated donor (MUD) children and they require short-term intensive care support. • Newer steroid-sparing agents for graft-versus-host disease (GVHD), reducing the dose of CD34 to less than 5 × 106/kilogram, and slow tapering of immunosuppression after the first 18 months help reduce morbidity and mortality due to GVHD and help optimize outcomes among the MUD HSCT recipients. Hematopoietic stem cell transplantation (HSCT) is the only curative option available for patients with thalassemia major in India with increasing access to alternate donor transplantation for patients with no matched family donor. We aimed to analyze the impact of family and alternate donor HSCT on morbidity and mortality post-HSCT. We conducted a retrospective study in the department between July 2007 and December 2018 where all children who underwent HSCT for thalassemia major were included. A total of 264 children were included with a median age of 6 years (male/female, 1.4:1). The graft source was matched related donor (MRD) (76%; parent 15%, sibling 85%) and matched unrelated donor (MUD) (22%). All children received a myeloablative conditioning regimen with treosulfan/thiotepa/fludarabine in 93% and busulfan/cyclophosphamide in 7%. The source of stem cells was peripheral blood in 61%, bone marrow in 38%, and umbilical cord blood in 3%. The incidence of bacteremia was 14% versus 25% in MRD versus MUD groups. There was a higher incidence of posterior reversible encephalopathy syndrome (PRES) in the MUD group (10% versus 3%). Engraftment occurred in 97% with a higher trend toward mixed chimerism in the MRD group (12% versus 2%). When indicated, whole-blood donor lymphocyte infusion was used to ensure complete chimerism in children in the MRD group. A statistically significant difference was found in the incidence of graft versus host disease (GVHD), both acute and chronic between the MUD versus MRD groups, 60% versus 20% and 41% versus 17%, respectively (P =.001). Similarly, immune cytopenia and cytomegalovirus reactivation were also significantly higher in the MUD group, 27% versus 1.4% and 25% versus 2%, respectively (P =.001). Thalassemia-free survival in our cohort was 96%, 94%, and 84% with a median follow-up of 65 months in the matched sibling donor, matched family donor, and MUD groups, respectively. Overall survival of 95% and 90% with a median follow-up of 65 months was noted in those who underwent transplantation less than and greater than 7 years of age, respectively. MUD transplantation for patients with thalassemia major involves specific challenges such as PRES and unusual manifestations of GVHD such as immune cytopenia. Early interventions to optimize supportive care and measures to reduce GVHD are required to ensure survival rates of over 90%. [ABSTRACT FROM AUTHOR]

• The mean femoral neck bone mineral density (BMD) was lower in recipients of allogeneic hematopoietic stem cell transplantation. • Myeloablative conditioning had an adverse effect on BMD at the femoral neck. • Lumbar spine BMD was lower in the group that received total body irradiation. • The prevalence of sarcopenia was significantly higher in cases than in controls. • Calcium and vitamin D supplements are recommended in these patients. • Consider graded strength-training exercises to build muscle mass. The significant advancements made in the field of allogeneic hematopoietic stem cell transplantation (allo-HSCT) have ensured increased longevity in transplant recipients. However, they do have late effects that may adversely affect the endocrine system, bone health, and body composition. This study was undertaken to evaluate bone mineral density (BMD), trabecular bone score, and body composition in recipients of allo-HSCT and compare them with age, sex, and body mass index (BMI) matched controls. This was a cross-sectional study done in 63 cases and 65 matched controls. The mean femoral neck BMD was found to be lower in cases than in controls (0.777 [0.119] versus 0.846 [0.122] g/cm2, P =.002). Among cases, the mean BMD at the neck of femur was lower in patients who had received myeloablative conditioning compared with those who had received the nonmyeloablative regimen (0.731 [0.090] versus 0.802 [0.126] g/cm2, P =.014]. The mean (SD) bone density at the lumbar spine was significantly lower in the group that had received total body irradiation compared with the group that did not (0.930 [0.111] versus 0.993 [0.127], P =.044). Trabecular bone score did not differ between cases and controls (1.383 [0.877] versus 1.389 [0.750], P =.670). The lean mass was significantly lower (15.9 [2.4] versus 18.6 [4.8] kg/m2, P <.001) and the prevalence of sarcopenia (42% versus 11%, P <. 001) significantly higher in cases than in controls. Normal-weight obesity was also noted to be higher among those with sarcopenia than in those without (12/26 versus 5/36; P =.009). The procedure of allo-HSCT may thus cause an impairment of bone health and alterations in body composition well after the cure of the primary disease. [ABSTRACT FROM AUTHOR]

Introduction: Autologous Stem Cell Transplant (ASCT) provides long periods of progression-free-survival in multiple sclerosis (MS). This is an observational study to demonstrate the safety of ASCT in MS patients at a transplant center in North India using a lymphoablative regimen.Materials and Methods: MS patients > 18 years referred by a neurologist or who came of their own volition were evaluated. Kurtzke Expanded Disability Status Scale (EDSS) score was calculated and those with a score of >7 were excluded. Informed written consent was taken. Mobilization was done with G-CSF with prednisolone to prevent disease flare-up. A minimum of 2 × 106 CD34 cells/kg was collected. Conditioning regimen consisted of rabbit ATG and cyclophosphamide. Rituximab 375 mg/m2 was given to prevent EBV reactivation and disease relapse. Antibiotic prophylaxis was given with levofloxacin, fluconazole, and valacyclovir. Any persistent change in EDSS scores ≥0.5 was considered significant.Results: Twenty patients were included. Seven patients had positive urine cultures prior to transplant and were treated before starting any chemotherapy. Majority patients were women (13/20). All patients developed febrile neutropenia, which was managed as per department policy. There was no mortality. Subjective symptoms improved in all patients. EDSS score improved in 6/19 patients (5/6 with RRMS) with no disease progression in any patient at a median follow-up duration of 242 days.Conclusion: ASCT can be done safely for patients with relatively high EDSS scores with additional precautions for screening for infections. RRMS patients with the active disease show most improvement. SPMS patients may not show significant improvement in the short term. [ABSTRACT FROM AUTHOR]

β-thalassemia is a common single-gene disorder in India, with hematopoietic stem cell transplantation (HSCT) being the only cure. HSCT with matched unrelated donor is less successful, whereas finding a human leukocyte antigen (HLA)-matched related donor is difficult. Preimplantation genetic testing for monogenic diseases (PGT-M) with HLA matching is a novel option to have a matched sibling for HSCT for couples having an affected child. We present the first such case report in India. A couple, both carriers of β-thalassemia and having an affected son, underwent PGT-M with HLA matching combined with preimplantation genetic testing for aneuploidies of embryos to have a β - thalassemia-free child. This resulted in birth of a 10/10 HLA-matched sibling. [ABSTRACT FROM AUTHOR]

Haploidentical stem cell transplantation (haplo SCT) has emerged as an acceptable alternative to matched family donor transplantation for children diagnosed to have primary immune deficiency disorders (PIDs). We present data over 4 years on the challenges and efficacy of unmanipulated T cell replete haplo SCTs with post-transplant cyclophosphamide (PTCy) in children diagnosed to have PIDs. We performed a retrospective study in the pediatric blood and marrow transplantation unit where all children less than 18 years of age diagnosed to have PIDs and who underwent haplo SCT with PTCy from January 2014 to February 2018 were included in the study. Of the 16 transplants included in the study, 5 children were diagnosed to have Wiskott-Aldrich syndrome, 3 with congenital hemophagocytic lymphohistiocytosis, 2 each with Griscelli syndrome and Mendelian susceptibility to mycobacterial diseases, and one each with Chediak-Higashi syndrome, ORAI 1 mutation immune deficiency, severe combined immune deficiency, and Hyper IgM syndrome. The source of stem cells was PBSC in 62.5% and bone marrow in 32.5%. Engraftment by day 16–21 post hematopoietic stem cell transplantation was achieved in 75% transplants with 91% of these remaining in sustained complete chimerism. Acute skin and gut graft versus host disease of grade 2–3 were noted in 50% transplants and cytomegalovirus (CMV) reactivation in 43.7% transplants. One child with congenital HLH succumbed to refractory CMV, adenovirus, and BK virus infection. Cytokine release syndrome (CRS) was noted in 75% transplants with 2 children succumbing to the illness. Tocilizumab was successfully used early in one child. Overall mortality was found to be 37.5% with overall survival of 62.5% with a median follow-up of 23.3 months. In resource limited settings, PTCy has the potential to provide a cost-effective advantage in terms of accessibility of this curative procedure among children with PIDs. [ABSTRACT FROM AUTHOR]

Background: Hematopoietic progenitor cell transplantation (HPCT) is used as a definitive treatment in hematological malignancies. For a successful HPCT, the donor and recipient should have matching human leukocyte antigens (HLAs). About 25% of patients have a chance of finding matching HLA within family, while rests 75% are dependent on voluntary stem cell donor. Globally, there are 75 stem cell registries with more than 30 million donors registered among which India represents 0.36 million. Therefore, finding a stem cell donor for Indian patient is quite difficult. The aim of the present study is to discuss the significance of voluntary stem cell donor recruitment drive and also to guide the drive organizers and their team for effectively organizing the drive to increase the database of such donors. Materials and Methods: Voluntary stem cell donor recruitment drives are conducted to spread awareness among the people and motivate them to register as a donor. Once the donors have given their consent, the sample is taken and sent to laboratory for HLA typing and the result is uploaded in World Marrow Donor Association, an international association of member to find the best possible matches for patients with hematological disorders. Results: Genebandhu has organized over 127 recruitment camps since 2012 and recruited 13,000 voluntary stem cell donors. HLA typing of 7446 donors has been completed. Out of this small number of typed donors, 11 lifesaving HPCTs have been successfully facilitated. Conclusions: Here, we have demonstrated guidelines along with steps to organize voluntary stem cell donors recruitment drive that is needed to increase number of donors, thus increasing significantly the chances of saving many vital lives. [ABSTRACT FROM AUTHOR]

The article examines the use of hematopoietic stem-cell transplantation (HSCT) as an appropriate tool to cure patients in India suffering from hematological disorders. Topics covered include data on disease prevalence for diseases where HSCT can offer a cure, the high proportion of patients not pursuing this treatment due to financial constraints, and efforts that are being made to introduce techniques that can reduce costs of HSCT.

Abstract: Hematopoietic stem cell transplantation (HSCT) remains the only curative treatment in patients with β‐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. [ABSTRACT FROM AUTHOR]