Imatinib, a tyrosine kinase inhibitor has improved survival in pediatric patients with Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia. There are no formal drug interactions listed between methotrexate and tyrosine kinase inhibitors. Four pediatric patients with Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia had delayed methotrexate clearance during their first cycle of high-dose methotrexate while receiving imatinib, resulting in acute kidney injury. For subsequent high-dose methotrexate cycles, imatinib was withheld resulting in decreased acute kidney injury, shorter time to methotrexate clearance, less toxicity, and shorter hospitalizations. For pediatric patients with acute lymphoblastic leukemia receiving imatinib, we recommend escalated supportive care measures including increased hyperhydration and leucovoruin frequency. For patients with toxicities secondary to delayed clearance or need for glucarpidase, we recommend holding imatinib with subsequent high-dose methotrexate courses.
BackgroundCryptococcal infections have been mostly associated with immunocompromised individuals, 80–90% of whom have been HIV-positive patients. Increasingly, cryptococcal infections are being reported in cirrhotic patients who are HIV-negative. The underlying immunologic defects in cirrhotic patients seem to play an important role in predisposing them to cryptococcosis and affecting their morbidity and mortality.Case presentationWe present a case of disseminated cryptococcosis in an HIV-negative patient with underlying cirrhosis, who had rapid worsening of his hyponatremia with renal failure and was unable to recover, despite aggressive measures.ConclusionCryptococcus is a more common culprit of infections seen in cirrhotic patients than what it was previously known, and a high index of suspicion is required to diagnose these patients. Identification of poor prognostic factors, early diagnosis and intervention is crucial in the management of these patients.
Background: Donor lymphocyte infusion (DLI) is often used to treat leukemic relapse after hematopoietic cell transplantation (HCT). However, the relationship between outcomes and distinct DLI cellular composition has not been previously reported. Additionally, there are limited published data on efficacy in pediatrics. We evaluated whether DLI cellular content and development of graft-versus-host disease (GVHD) impacted disease and influenced overall survival (OS) in children receiving DLI for recurrent leukemia.
Methods:We performed an Institutional Review Board-approved, retrospective study investigating all consecutive DLIs given to patients at the Children's Hospital of Wisconsin between 1980 and 2018. Analyses were conducted using Mann-Whitney, Fisher exact, and chi-square tests.Results: Thirty patients ≤20 years old with hematologic malignancies (myeloid [AML/MDS/ CML/JMML], n = 23; lymphoid [ALL], n = 7) received DLI to treat post-transplant relapse. We found no significant difference in OS or development of GVHD based on CD3, CD4, CD8, CD56, or CD19 DLI cellular composition. With a median follow-up of 0.69 (range, 0.04-16.61) years, OS at five years was 32% ± 9%. The lymphoid group had a five-year survival rate at 71% ± 17% compared with the myeloid group at 22% ± 9%, although not statistically significant (P = 0.11). The development of GVHD did not affect OS (P = 0.62).
Conclusion:Here, we report a single-center, long-term experience of pediatric DLIs. Surprisingly, many children with ALL were able to achieve durable remissions. Although cellular composition did not have a significant effect on GVHD or OS in our small study, engineering DLI products to maximize specific effector cell populations could be one strategy to improve efficacy.
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