Hepatocellular carcinoma as a complication of chronic Budd-Chiari syndrome (BCS) in a child.

Hepatocellular carcinoma (HCC) is an extremely rare long-term complication of Budd-Chiari syndrome (BCS) which may occur due to long-term venous congestion causing fibrosis, cirrhosis and subsequent hepatocellular dysplasia or anaplasia. This complication is even rarer in paediatric BCS and warrants early diagnosis for a favourable prognosis. Benign regenerative nodules seen with BCS are difficult to differentiate from malignant nodular lesion of HCC, thereby making serial imaging less sensitive for early diagnosis of HCC in BCS. Surveillance guidelines like adults do not exist in monitoring chronic paediatric BCS due to rarity of this complication. Six monthly serum alpha-fetoprotein monitoring in addition to radiological surveillance improves the sensitivity of early detection of HCC transformation in BCS and should be the way ahead in paediatric BCS as well. We describe a paediatric patient who presented with advanced HCC after 25-month follow-up for BCS.

Vascular Tumor with Kasabach Merritt Phenomenon Treated with Steroids and Vincristine: A Retrospective Study.

Vascular tumours (VT) with Kasabach-Merritt phenomenon (KMP) are rare and aggressive tumors. In absence of evidence based treatment guidelines, we studied varied presentation and response to therapy with vincristine and steroids in VT with KMP at our center. In this retrospective observational study, infants with a symptomatic/disfiguring rapidly growing VT with features of KMP were included. Demographic, treatment and outcome data was retrieved from patient file. Complete response (CR) was defined as complete clinical regression of VT with normalization of coagulopathy and thrombocytopenia. Partial response (PR) was defined as decrease in size of VT by more than 80%, absence of clinical bleed with normalization of coagulopathy and platelet count > 50,000/cumm. Five infants (2-male, 3-female) with age range (0-7 month) treated with daily prednisolone and weekly vincristine were included. The location of VT was: face (2), hemi-thorax (2) and urinary bladder (1). Four of five infants showed PR within two months; while two of these attained CR to treatment. There were no significant adverse effects over 9-32 (range) month follow-up. Two children (one in PR, one immediately after presentation) succumbed to intra-cranial hemorrhage. Combination therapy of steroids with vincristine is effective and safe in management of VT with KMP.

Clinicodemographic profile, management, and treatment outcomes in advanced retinoblastoma at a tertiary care center in North India.

PURPOSE: The study was undertaken to look into the clinicodemographic profile, management, and clinical outcomes of advanced retinoblastoma at a tertiary care center. METHODS: A prospective cohort study was conducted from Jan 2019 to Dec 2022. Forty-two patients of intraocular advanced retinoblastoma were assessed. The treatment protocol was formulated based on size, extension of tumor, and laterality. Primary outcome measure was response to the treatment in terms of regression of tumor and seeds and no evidence of recurrence after 12 month in enucleated eyes. Secondary outcome measures were complications like implant exposure, metastasis, and death associated with each treatment modality. RESULTS: The mean age of the study group was 13 months. The most common presentation was leukocoria with diminished vision. Most of the patients had group E retinoblastoma ( n = 40, 95%) as per the International Classification of Retinoblastoma. In 12 patients with group E retinoblastoma, primary enucleation was performed and in six patients, secondary enucleation was done, in which initially, globe salvage treatment was tried. In 30 patients, globe salvage treatment was attempted and we could manage to save 23 eyes. The most common treatment modality was intra-arterial chemotherapy using a triple-drug regimen. One patient developed intracranial spread and died due to systemic metastasis during the follow-up period. CONCLUSION: The current study showed that globe salvage is possible in advanced retinoblastoma if appropriate therapy is instituted depending upon the extent of the tumor and availability of latest treatment modalities. Intra-arterial chemotherapy using triple drugs can be offered as a first-line therapy in advanced unilateral retinoblastoma as it has been found to be very effective in the present study.

Synchronous presentation of ETV6::RUNX1 fusion positive concordant B-acute lymphoblastic leukaemia in identical twin toddlers.

Concordant leukaemia in identical twins is rare. The likelihood of concordance of leukaemia in twins is near 100% in infancy, around 10% from 1 to 6 years of age, and rare at a later age with variable latency. Reporting of new cases of concordant leukaemia in twins is encouraged to contribute to data pool of this infrequent but exceptional condition; especially when the theories with respect to evolution, natural history and molecular evidence explaining concordant leukaemia in identical twins are still evolving.We discuss identical pair of monochorionic twin toddlers who were detected to have pallor and blood investigations revealed pancytopenia. Further work up including bone marrow studies revealed synchronous diagnosis of B-acute lymphoblastic leukaemia (B-ALL) with ETV6::RUNX1 fusion. Synchronous presentation of concordant leukaemia in identical twins is extremely rare. Index twins are the only second set of twins and first one beyond infantile age with synchronous presentation of B-ALL.

Complete resolution of primary myelofibrosis in an infant with steroids and hydroxyurea.

Paediatric primary myelofibrosis (PMF) is exceedingly rare and distinct compared with adult PMF. It is characterised by peripheral blood cytopenias, leucoerythroblastosis, reticulin fibrosis, extramedullary haematopoiesis and hepatosplenomegaly. In the absence of laid down diagnostic criteria, the diagnosis is largely of exclusion. Though early haematological stem cell transplant (HSCT) remains the treatment of choice, spontaneous remission or remission with steroids and/or cytoreductive agents is described in around 20% of cases of paediatric PMF. Moreover, HSCT in paediatric PMF is associated with high mortality (30%-45%). Therefore, it may be prudent to consider a trial of steroids and/or cytoreductive agents in all transfusion-dependent paediatric PMF while considering HSCT and ongoing bone marrow donor search. We describe one such infant with PMF who had complete remission of clinical and haematological parameters with a combination therapy of steroids and hydroxyurea.

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

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

Impact of pre-hydration duration on high-dose methotrexate induced nephrotoxicity in childhood acute lymphoblastic leukaemia in resource constraint centers: a randomized crossover study.

PURPOSE: Hydration before starting high-dose methotrexate (HD-MTX) ensures good renal perfusion and alkaline urinary pH. The duration of pre-hydration is not uniform across protocols. We compared 6-h versus 12-h of pre-hydration for HD-MTX therapy in childhood acute lymphoblastic leukaemia (ALL) at our centre where serial MTX level monitoring is not feasible. METHODS: This randomised cross-over study consecutively enrolled children < 12 years with ALL receiving HD-MTX. Children with pre-existing renal disease or those exposed to nephrotoxic drugs were excluded. Two groups receiving 6-h versus 12-h pre-hydration on alternate basis in same patient (each exposed to four cycles of 2-5 g/m2 of HD-MTX) were compared for HD-MTX induced nephrotoxicity (primary outcome) and other HD-MTX toxicities (HMT) as per common terminology criteria for adverse events (CTCAE-4.0). HD-MTX was administered over 24 h as per BFM-protocol-2009. Solitary MTX levels at 36-h (MTX36) were outsourced and leucovorin (LV) was started at 36 h at 15 mg/m2/dose for 6-8 doses 6-hourly depending on MTX36. Hydration fluid was dextrose normal saline with sodium-bicarbonate and administered till last LV dose. RESULTS: Total 136 HD-MTX cycles in 34 patients (age range 5-144 months) were evaluated. Nephrotoxicity [2/68 (2.9%) in 6-h versus 1/68 (1.5%) in 12-h] and HMT incidence was comparable in two pre-hydration groups. Median MTX36 levels were not affected by duration of hydration irrespective of administered dose of HD-MTX. Median serum creatinine at baseline, post-pre-hydration and at 36-h post start of HD-MTX were comparable. CONCLUSION: Reduction of pre-hydration duration does not affect HD-MTX induced nephrotoxicity and MTX36 levels in children < 12 years.

Safety and outcome of ultrasound-guided tunneled central venous catheter in children with cancers from low middle-income country: A prospective study.

BACKGROUND: Central venous access devices (CVAD) are vital for cancer therapeutics in pediatric oncology. Tunneled vascular access devices (TVAD) are preferred in children for prolonged and frequent vascular access. Data on insertion, care, and complications of CVAD in children from low middle-income countries (LMIC) are scarce, heterogeneous, and retrospective. PROCEDURE: This prospective observational study on eligible children <12 years with pediatric malignancies requiring chemotherapy for minimum 6 months from diagnosis excluded children with mucosal bleeding, coagulopathy, and infections. TVAD insertion was ultrasound (USG) guided. Number of catheter-days, surgical and nonsurgical complications, and risk factors for catheter-related bloodstream infections (CRBSI) were noted TVAD removal due to complications, therapy completion, tumor progression, or death. RESULTS: Data from 61 of 86 eligible children with median age 42 months (range 1-144) were analyzed. Hematological malignancy and severe thrombocytopenia were seen in 37/61 (61%) and 18/61 (30%) children, respectively. First-attempt success rate was 74%. Surgical complications were seen in four of 61 (7%). Nonsurgical complications were seen in 33/61 (54%) children; CRBSI was commonest 24/61 (39%), causing removal of TVAD in 14/61 (23%). Incidence per 1000 catheter-days for CRBSI was 3.24. Antibiotic lock therapy could salvage nine of 24 TVAD with CRBSI. Thrombus and accidental removal was seen in six of 61 (10%) and four of 61 (7%). None of the studied risk factors were significantly associated with CRBSI. The mean insertion duration of TVAD was 121 ± 90 days. CONCLUSION: USG-guided TVAD insertion is safe and reliable way for chemotherapy administration with acceptable complications in children with malignancies in LMIC, including children with severe thrombocytopenia.

Grade 4 very severe hypertriglyceridaemia at diagnosis in a child with acute lymphoblastic leukaemia.

Dyslipidaemia is seen in nearly all cases of acute lymphoblastic leukaemia (ALL) at diagnosis, with mild hypertriglyceridaemia (HTG) in 61% and reduced high-density lipoprotein in 98% cases. HTG irrespective of severity is due to metabolic derangements associated with tumour cells turnover in haematological malignancies and is generally self-limiting. Very severe HTG with overt lipaemic serum is extremely rare at presentation in ALL. HTG is complicated by thrombosis, osteonecrosis and pancreatitis during induction chemotherapy for ALL with steroids and L-asparginase. A careful monitoring is required during induction chemotherapy in ALL when severe HTG is present at diagnosis. We present a female toddler with ALL, who presented with very severe HTG and grossly lipaemic serum. Her very severe HTG decreased to mildly raised HTG at the end of first week of induction chemotherapy. There was no further complication noticed during induction therapy.

Hypoalbuminemia and not undernutrition predicts high-dose methotrexate-induced nephrotoxicity in children with acute lymphoblastic leukemia in resource-constrained centers.

BACKGROUND: The standard practice to mitigate high-dose methotrexate (HD-MTX)-induced nephrotoxicity (HMN) in acute lymphoblastic leukemia (ALL) is to monitor levels until serum MTX falls below a predefined threshold. It is not feasible in most resource-constrained centers. Literature on the various factors affecting HMN in these centers is limited, retrospective, and heterogeneous. Though hypoalbuminemia has been postulated as a risk factor for HMN, the relationship of undernutrition with HMN has not been studied. PROCEDURE: This prospective observational study consecutively enrolled children < 12 years old with ALL receiving HD-MTX. Children with preexisting renal disease and exposed to nephrotoxic drugs two weeks preceding HD-MTX infusion were excluded. HD-MTX was administered over 24 hours (BFM-2009 protocol) with 12 hours of prehydration. Solitary MTX levels at 36 hours (MTX36) were outsourced, and 6-8 doses of leucovorin were given six-hourly. Hydration was continued till last dose of leucovorin. Various factors affecting HMN (rise in creatinine to 1.5 times baseline) were recorded: age, sex, type of ALL, risk group of ALL, first dose of MTX, dose of MTX, undernourishment, serum protein, and albumin along with C-reactive protein and MTX36 levels. RESULTS: Forty-four children who received 150 HD-MTX cycles were analyzed. HMN was seen in 14% of cycles. On univariate analysis, undernourishment, MTX36 levels, hypoproteinemia, and hypoalbuminemia were significantly associated with HMN. On multivariate analysis, hypoalbuminemia and MTX36 levels significantly predicted the development of HMN with odds ratios of 4.71 and 1.45. CONCLUSION: Hypoalbuminemia and solitary serum MTX levels predict HMN in centers where serial MTX level monitoring is not feasible.

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

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