Chronic graft versus host disease (cGvHD) is the most common cause for non-relapse mortality post allogenic hematopoietic stem cell transplant (HSCT). However, there are no well-defined biomarkers for cGvHD or late acute GvHD (aGvHD). This study is a longitudinal evaluation of metabolomic patterns of cGvHD and late aGvHD in pediatric HSCT recipients. A quantitative analysis of plasma metabolites was performed on 222 evaluable pediatric subjects from the ABLE/PBMTC1202 study. We performed a risk-assignment analysis at day+100 on subjects who later developed either cGvHD or late aGvHD after day 114 to non-cGvHD controls. A second analysis at diagnosis used fixed and mixed multiple regression to compare cGvHD at onset to time matched non-cGvHD controls. A metabolomic biomarker was considered biologically relevant only if it met all three selection criteria: a) p value ≤0.05, b) effect ratio of ≥1.3 or ≤0.75, and c) receiver operator characteristic AUC ≥0.60. We found a consistent elevation in plasma alpha-ketoglutaric acid before (Day + 100) and at the onset of cGvHD, not impacted by cGvHD severity, pubertal status, or previous aGvHD. In addition, late aGvHD had a unique metabolomic pattern at day+100 compared to cGvHD. Additional metabolomic correlation patterns were seen with the clinical presentation of pulmonary, de novo, and progressive cGvHD. Alpha-ketoglutaric acid emerged as the single most significant metabolite associated with cGvHD, both in the day +100 risk-assignment and later diagnostic onset analysis. These distinctive metabolic patterns may lead to improved subclassification of cGvHD. Future validation of these exploratory results are needed.

We present our data on granulocyte transfusions in children undergoing treatment for cancer and HSCT at our centre and their changing indications. In this retrospective observational analysis of children who received granulocytes from 2007 to 2015, we divided children receiving granulocytes into two groups-the first from January 2007 till December 2013 and the second from January 2014 till December 2015. This division is based on the change in our policy to use granulocytes within 48 h of septicemia as the incidence of drug resistant bacterial strains had increased at our centre. Data on 72 children with febrile neutropenia treated with 230 granulocyte infusions was analyzed. From 2007 to 2013 (n = 48/72), 27/48 (56 %) had culture proven sepsis of which 14 (51 %) were carbapenem resistant gram negative bacilli. 11 of the 27 children survived the crisis (41 %). We then changed our policy to transfuse granulocytes early during sepsis. From 2014 to 2015 (n = 24/72) 22 patients had culture proven sepsis (91 %) of which 20 had carbapenem resistant gram negative bacilli. 12/22 (54 %) with culture proven sepsis survived the episode. The survival rate improved from 41 % in first group to 54 % after early intervention with granulocytes ( value 0.0347). Despite the increased incidence of resistant bacteria during the period of 2014-2015, early use of granulocytes improved survival rate from 41 to 54 %. This intervention cannot be taken in isolation and needs to be offered early in parallel with appropriate antibiotics.

Optimal management of infectious complication is the biggest challenge in children receiving chemotherapy for acute myeloid leukemia (AML). We have analyzed the data of children undergoing AML induction chemotherapy at our center from 2002 to 2016 and found that Gram-negative infections are more predominant when compared to the published literature. There also has been a surge in multidrug-resistant (MDR) infections over the last 4 years, which has increased the need for supportive care and escalated the cost of care. We have introduced certain novel methods to combat MDR sepsis and decrease mortality rates.

We aimed to determine a correlation between cytomegalovirus reactivation post hematopoeitic stem cell transplantation (post-HSCT) with the type of graft source, defining children at risk. We analyzed data on children less than 18 years of age undergoing HSCT from 2002 to May 2016 (n = 464). Correlation between reactivation and graft source was analyzed statistically. Reactivation occurred in 3% of children with matched-related donor (MRD) transplants, 33.3% with unrelated peripheral blood stem cells, 17.4% with unrelated cords, and 36.5% (15/41) with mismatched or haploidentical grafts (P = <0.0001). MRD does not warrant weekly PCR, unlike unrelated or haploidentical donors, thus defining protocols for developing countries with limited resources.

Refractory/relapsed Langerhans cell histiocytosis (LCH) has a difficult course with a guarded prognosis. We used a novel protocol including six cycles of pulse dexamethasone and lenalidomide in four children with LCH refractory to first-line agents and courses of cladribine and cytarabine or single-agent cladribine. All four children completed the protocol without any significant adverse effects and remain in complete and durable remission 15-18 months posttreatment. The novel protocol we propose for relapsed/refractory LCH is cost-effective and outpatient-based with durable remission and minimal toxicity. This is particularly suited for resource-limited settings.