Eric S. Schafer

Use of allopurinol in children with acute lymphoblastic leukemia to reduce skewed thiopurine metabolism

Mercaptopurine (6‐MP), a critical component of acute lymphoblastic leukemia (ALL) therapy, is metabolized to 6‐thioguanine (6‐TGN) which is responsible for its anti‐leukemic effect, and to 6‐methylmercaptopurine nucleotides (6‐MMPN/6‐MMP) which can be hepatotoxic. Some patients preferentially metabolize 6‐MP to 6‐MMPN which may increase the risk of liver injury, reduce serum levels of 6‐TGN and potentially increase the risk of relapse. The addition of allopurinol to oral 6‐MP has been shown to optimize metabolism towards 6‐TGN in patients with inflammatory bowel disease (IBD); however, this use has not been reported in patients undergoing treatment for ALL. Pediatr Blood Cancer 2014;61:1114–1117.

Persistent Multiyear Control of Relapsed T-Cell Acute Lymphoblastic Leukemia With Successive Donor Lymphocyte Infusions: A Case Report.

There are few therapeutic options for patients with T‐cell acute lymphoblastic leukemia (T‐ALL) who have recurrent disease after initial matched sibling hematopoietic stem cell transplantation. While a second hematopoietic stem cell transplant (HSCT) from a haploidentical donor offers the conceptual possibility of greater graft versus leukemia effect, there is minimal literature to describe the efficacy of this approach in recurrent pediatric T‐ALL. We present the case of a now 9‐year‐old female in whom second haploidentical HSCT, followed by successive donor lymphocyte infusions in response to minimal residual disease reemergence, has led to 3+ years of ongoing disease control without graft versus host disease and excellent quality of life.

Successful Treatment of Recurrent Autoimmune Cytopenias in the Context of Sinus Histiocytosis With Massive Lymphadenopathy Using Sirolimus.

Sinus histiocytosis with massive lymphadenopathy (SHML), or Rosai–Dorfman disease (RDD), is a non‐neoplastic, lymphoproliferative disorder that usually resolves spontaneously or with minimal conventional chemotherapy. Rarely, SHML can be associated with autoimmune findings. Such cases are often treatment resistant and have high rates of morbidity and mortality. We present a case of a patient with long‐standing autoimmunity in the context of SHML, dependent on standard‐treatment until he was transitioned to novel monotherapy with sirolimus. Sirolimus treatment resulted in a complete remission, now sustained after discontinuation of all treatments for over 23 months, with no observable long‐term sequelae. Pediatr Blood Cancer

Treatment-related sinusoidal obstruction syndrome in children with de novo acute lymphoblastic leukemia during intensification

PurposeSinusoidal obstruction syndrome (SOS), also known as veno-occlusive disease, has been described following treatment of acute lymphoblastic leukemia (ALL) with the anti-metabolite 6-thioguanine (6-TG). Previous studies incorporating daily 6-TG into maintenance chemotherapy demonstrated a high incidence of SOS, typically presenting after prolonged exposures to 6-TG. 6-TG continues to be used as a single, 14-day burst during intensification; however, SOS associated with brief courses of 6-TG is poorly described. We aim to describe this rare though clinically significant phenomenon.MethodsChildren with 6-TG-related SOS were retrospectively identified from 680 de novo patients with ALL at Texas Children’s Cancer Center over 8 years. Clinical characteristics and outcomes are described.ResultsTen (1.5%) patients were identified with SOS. No predominant sex, ethnicity, or race was noted. SOS was diagnosed 16.5 (6–42) days from starting 6-TG. Isolated thrombocytopenia (IT) was noted in 9/10 patients and presented a median of 5 days prior to SOS. Refractoriness to platelet transfusions was noted in 8/10 patients, presenting a median of 2 days prior to SOS. Most patients were otherwise clinically stable outpatients upon presenting with IT or transfusion refractoriness. Fever was noted in 7/10 patients at diagnosis and 6/10 had documented or suspected infection within 14 days of SOS. Two patients died, while eight fully recovered. Intermediate thiopurine methyltransferase genotype was noted in 5/8 patients with data available.ConclusionSOS following short courses of 6-TG in DI is clinically distinct from SOS following prolonged courses of 6-TG in maintenance, particularly in its early presentation and outcomes.

A phase 1 study of eribulin mesylate (E7389), a novel microtubule‐targeting chemotherapeutic agent, in children with refractory or recurrent solid tumors: A Children's Oncology Group Phase 1 Consortium study (ADVL1314)

Eribulin mesylate is a novel anticancer agent that inhibits microtubule growth, without effects on shortening, and promotes nonproductive tubulin aggregate formation. We performed a phase 1 trial to determine the dose‐limiting toxicities (DLTs), maximum tolerated or recommended phase 2 dose (MTD/RP2D), and pharmacokinetics (PK) of eribulin in children with refractory or recurrent solid (excluding central nervous system) tumors.

Evaluation of aprepitant for acute chemotherapy-induced nausea and vomiting in children and adolescents with acute lymphoblastic leukemia receiving high-dose methotrexate

Chemotherapy‐induced nausea and vomiting (CINV) negatively impacts patients’ quality of life. The emetogenicity of high‐dose methotrexate in children and adolescents with cancer is incompletely characterized. At our institution, a number of patients with acute lymphoblastic leukemia (ALL) have received aprepitant with courses of high‐dose methotrexate after poor CINV control with prior courses.

Hispanic ethnicity as a risk factor for requiring glucarpidase rescue in pediatric patients receiving high-dose methotrexate

Anjum B. Khan , Rachel Kesse-Adu, Cormac Breen, Patrick B. Murphy, John Chambers, Paul Holmes, Joanna Howard Department of Haematology, Guy’s and St Thomas’ NHS Foundation Trust, London, UK Department of Nephrology, Guy’s and St Thomas’ NHS Foundation Trust, London, UK Lane Fox Respiratory Unit, Guy’s and St Thomas’ NHS Foundation Trust, London, UK Division of Asthma Allergy and Lung Biology, King’s College London School of Medical Education, London, UK Department of Cardiology, Guy’s and St Thomas’ NHS Foundation Trust, London, UK Cardiovascular Division, King’s College London, UK Department of Neurology, Guy’s and St Thomas’ NHS Foundation Trust, London, UK