Haploidentical Stem Cell Transplantation: Half Match but More Hope!-Single Centre Experience from Western India.

With the success of post-transplant cyclophosphamide based platform and improved clinical care, the number of haploidentical stem cell transplants (HaploSCT) have surged over the last decade. However, data from India is scarce. We aimed to evaluate the outcome of haploSCT at our centre. Since the inception of government schemes, many patients at our centre are able to undergo transplantation at subsidized cost. We conducted a retrospective analysis of the haploidentical transplants performed between January 2015 and November 2022. Fifty patients were eligible for this study. Patient details were obtained from case files. The graft versus host disease (GVHD) prophylaxis was post-transplant Cyclophosphamide (PTCy) with Mycophenolate-mofetil and Cyclosporine/tacrolimus/sirolimus. All patients were transfused peripheral blood stem cells from donors. Post-transplant, patients continued regular follow up as per schedule. Supportive care was given as per unit protocol. Overall survival (OS) was calculated using the Kaplan-Meier method. Fifty patients underwent haploSCT. A total of fifty patients with a median age of 20 years (range 3-53 years) underwent haploidentical HSCT from a family donor. Twenty three (46%) patients were > 18 years age and 82% were males. Indications for transplant included both benign and malignant hematological diseases. Most common conditioning regimen used was Fludarabine + Busulphan + Cyclophosphamide (n = 38, 76%). Thirty five patients (70%) engrafted successfully. In the patients who had successful engraftment, the median time to neutrophil engraftment was 16 days (range 10-20 days) and platelet engraftment was 18 days (range 10-32). Fourteen patients developed acute GVHD (28%), and three patients developed chronic GVHD (6%). The median follow-up was 30 months and the two-year OS was 43% with a median OS of 17 months. Twenty-one (adult = 9, pediatric = 12) out of 50 patients (42%) are alive and on regular follow-up. HaploSCT with a PTCy platform is a cost-effective, promising modality of treatment in patients who have no suitable matched donors and are not affording matched unrelated transplants. At our centre, we were able to achieve acceptable results with use of generic medications at affordable cost. Transplant Related Mortality (TRM) rates were comparable to other centres, however, multi-drug resistant bacterial infection remains a challenge in performing haploidentical HSCT in developing countries.

Clinicopathological and oncological outcomes in upper extremity Ewing's sarcoma: A single institutional experience.

Background: Ewing's sarcoma is highly aggressive bone tumor having predilection for younger age groups with t (11,22) translocation, recombines the FLI-1 and EWS genes on chromosome 22. This disease requires multi-disciplinary treatment withneo-adjuvant chemotherapy followed by surgery or radiotherapy and adjuvant chemotherapy. This study was aimed to assess the demographic distribution, clinical behaviour and oncological outcome of Ewings Sarcoma involving upper extremity. Methods: From 2015 to 2022, 45 patients of upper extremity Ewing's sarcoma underwent treatment at a territory cancer centre. A total of 26 patients treated with surgical management were included in the study comprising 15 males (57.7 %) and 11 females (42.3 %). Mean age of presentation was 26 years (3-43 years). The most common site for Ewings sarcoma of upper extremity was Humerus(42 %) followed by Scapula(27 %), Radius(15 %), Ulna(8 %), Metacarpals(4 %) and Clavicle(4 %). Out of 26 cases, 19 (73%) underwent limb salvage surgery and 7 (27%) underwent ampuation surgery. Results: In limb salvage group reconstruction with Extra-corporeal radiotherapy (ECRT), Ulna centralization, Megaprosthesis and 3D printed scapula was performed following wide resection of tumor. In Amputation group ray resection in one case and forequarter amputation was performed in six cases. Mean serum LDH value was 335 IU/L (2.3X Normal value) and serum albumin was 4.04 gm/dl. Mean tumour necrosis after neo-adjuvant chemotherapy was 68 %. Out of 26 cases, 19(73 %) cases underwent limb salvage and 7 patients underwent amputation surgery. Out of 26, 13 (50 %) patients developed metastasis on follow up. The Event free survival (EFS) in current study was 70 % at 12 months and 40 % at 24 months. Mean Event free survival (EFS) in current study was 33.5 months (22.3-44.6) and Median Event free survival (EFS) in current study was 25 months (19.7-30.2). Conclusion: This study characterises demographic and oncologic outcomes of upper extremity ewings sarcoma in Indian subpopulation. Pain and swelling were prominent clinical findings at presentation in patients with upper extremity Ewing's sarcoma. The survival rate following limb salvage surgery in Ewings sarcoma of upper extremity was comparable to that of patients with amputation surgery. Ewings sarcoma of upper extremity was associated with higher LDH level which was raised more than twice the normal range and can led to worse oncologic outcomes. A comparative study on upper extremity and lower extremity ewings sarcoma will be of help to improve literature on this rare disease.

Clinical profile and outcome of children with anaplastic large cell lymphoma treated with short-course chemotherapy - ten years experience from a tertiary care center in a LMIC.

Anaplastic large-cell lymphoma (ALCL) constitutes 10-15% of non-Hodgkin lymphoma in children. With short-course chemotherapy, outcome has improved up-to 90% in developed-countries. There is limited-data on outcome of pediatric ALCL treated with ALCL99 protocol from low-middle income countries. Children ≤14 years, diagnosed with ALCL between 1st January 2007 and 31st December 2016 were analyzed. Details regarding clinical-presentation and treatment were recorded and outcome was analyzed. Fourteen-children were diagnosed. Median-age was 114 months (range 24 - 162 months). Male:female ratio was 3.6:1. Stage-I, II and III disease was seen in three (21.4%), three (21.4%), and eight (57.1%) children, respectively. Low, standard and high-risk disease was seen in two (14.2%), six (42.9%) and six (42.9%), respectively. All children were treated using ALCL99 protocol. Three (21.4%) children had disease-progression/relapse and five (35.7%) died (three from treatment-related mortality, and two from disease). At median follow-up of 54-months, four-year EFS and OS were 64.3% and 64.3%, respectively. Log-rank test demonstrated female gender (p = 0.005), stage-III disease (p < 0.001), visceral-organ involvement (p = 0.035), high-risk disease (p = 0.016) and, serum albumin ≤3.5 g/dL (p = 0.031) associated with significantly worse 4-year EFS. Cox-regression analysis demonstrated female gender associated with poor EFS (p = 0.02) and female gender and visceral-organ involvement associated with poor OS (p = 0.02, p = 0.011, respectively). Good survival could be achieved for children with ALCL using uniform treatment protocol in a resource-limited setting, especially among low and standard-risk children. Female-sex, high-risk disease, stage-III disease, visceral organ involvement and low albumin levels were associated with poor outcome, however these findings need to be corroborated in larger studies.

Methotrexate-Induced Leukocytoclastic Vasculitis.

Erythematous tender cutaneous lesions developed in a 10-year-old child of acute leukemia receiving oral methotrexate and 6-mercaptopurine during maintenance phase of chemotherapy. She was also found to have coagulopathy and transaminitis. Differential clinical diagnosis included infectious processes, pyoderma gangrenosum, connective tissue disorders like rheumatoid neutrophilic dermatitis, and drug-induced side effects. Oral methotrexate was withheld following which the lesions subsided. Skin biopsy revealed a diagnosis of leukocytoclastic vasculitis. Cutaneous vasculitis is a rare side effect of methotrexate and its possibility should be considered in any patient who develops skin lesions while being receiving chemotherapy.

Oral Vitamin D Supplementation to Mothers During Lactation-Effect of 25(OH)D Concentration on Exclusively Breastfed Infants at 6 Months of Age: A Randomized Double-Blind Placebo-Controlled Trial.

Background: Exclusively breastfed infants are at risk of vitamin D deficiency. Objective: To find out proportion of exclusively breastfed infants having serum 25(OH)D concentration <11 ng/mL at 6 months of age with or without oral supplementation of vitamin D3 to lactating mothers. Methods: Randomized placebo-controlled study included 132 mothers and infants divided into two groups. Mothers received either vitamin D3 60,000 IU between 24 and 48 hours postpartum and at 6, 10, and 14 weeks amounting to 240,000 IU of vitamin D3 or placebo. Serum 25(OH)D concentration in the mothers was measured at recruitment and that of infants, at birth and 6 months. Infants were evaluated for rickets at 6 months. Findings: Total 114 mother-infant dyads followed. Subjects in both groups were comparable in basic characteristics. At 6 months of age, serum 25(OH)D concentration in infants was 18.93 (5.12) ng/mL in the intervention group and 6.43 (3.76) ng/mL in the control group (mean difference = 12.5; 95% CI = 10.80-14.17; p < 0.001) and vitamin D deficiency and insufficiency was corrected in 93.1% and 38% infants, respectively, in the intervention group. There was no change in the vitamin D status of infants in the control group. In 60.3% infants (RR = 0.519; 95% CI = -0.485 to 0.735) of the intervention group 25(OH)D concentration was <20 ng/mL at 6 months of age. Six infants in the control group suffered from biochemical rickets. Radiological rickets developed in one infant in the intervention group and two infants in the control group. Conclusion: Serum 25(OH)D concentration of exclusively breastfed infants rise significantly when mothers are orally supplemented with 240,000 IU of vitamin D3 during lactation in comparison with the infants of unsupplemented mothers with 94.6% and 48.1% reduction in the risk of vitamin D deficiency and insufficiency, respectively, at 6 months of age.

Primary Mediastinal Large B-Cell Lymphoma in a Child Presenting With Superior Mediastinal Syndrome and Chylous Pleural and Pericardial Effusion.

Primary mediastinal (thymic) large B-cell lymphoma is an aggressive B-cell lymphoma. It comprises <3% of all pediatric non-Hodgkin lymphomas (NHLs). Primary mediastinal (thymic) large B-cell lymphoma usually presents with serous pleural effusion, but presentation with chylous pleural and pericardial effusions is rare. We present a child who presented with features of a superior mediastinal syndrome. Biopsy of the mediastinal mass confirmed the diagnosis of large B-cell lymphoma. In view of nonimprovement of respiratory distress with chemotherapy and persistence of features of superior mediastinal syndrome, the child was evaluated and found to have massive pleural and pericardial effusion on imaging. Therapeutic thoracentesis and pericardiocentesis revealed chylous nature of the fluid.

Rotavirus Gastroenteritis Associated with Encephalopathy, Myositis, Transaminitis and Hypoalbuminemia.

Rotavirus is a common cause of acute gastroenteritis in children. Manifestations of rotavirus gastroenteritis beyond gastrointestinal tract are rare. Rotavirus has been reported to be associated with encephalopathy, myositis and elevated liver enzymes; but simultaneous presentation of all these conditions in the same child is extremely rare. The authors report a case of 17-mo-old girl who presented with acute rotavirus gastroenteritis with G3 + G9P[8] strain associated with hypernatremia, encephalopathy, myositis, transaminitis and hypoalbuminemia. Child had complete recovery with no neurological sequalae on follow-up, and liver enzymes and albumin returned to normal. The authors suggest that rotavirus infection should be considered in the differential diagnosis of a child with encephalopathy or myositis, particularly if associated with acute diarrhea.