Orly Klein, MD

View details for DOI 10.3390/jcm12134229

Abstract

INTRODUCTION: Total body irradiation (TBI) is an important component of many conditioning regimens for hematopoietic stem cell transplantation (HSCT), most commonly used in pediatric and adolescent/young adult (AYA) patients. We aimed to evaluate outcomes and toxicities among pediatric and AYA patients treated with TBI utilizing volumetric modulated arc therapy total body irradiation (VMAT-TBI).METHODS: We reviewed pediatric and AYA patients treated with VMAT-TBI at our institution from 2019 to 2021. Data on patient and disease characteristics, treatment details, outcomes and toxicities were collected. Overall survival (OS) and relapse-free survival (RFS) were analyzed using the Kaplan-Meier method.RESULTS: Among 38 patients, 16 (42.1%) were treated with myeloablative regimens and 22 (57.9%) with nonmyeloablative regimens. Median age was 7.2 years (range: 1-27) and median follow-up was 8.7 months (range: 1-21). Lungs Dmean was 7.3 0.3Gy for myeloablative regimens (range: 6.8-7.8). Kidneys were spared to average mean dose of 71.4 4.8% of prescription dose. Gonadal sparing was achieved for patients treated for nonmalignant diseases to Dmean of 0.7 0.1Gy. No patient experienced primary graft failure; one (2.6%) experienced secondary graft failure. The most common grade 1-2 acute toxicities were nausea (68.4%) and fatigue (55.3%). Mucositis was the most common grade 3-4 acute toxicity, affecting 39.5% of patients. There were no cases of pneumonitis or nephrotoxicity attributable to TBI.CONCLUSION: VMAT-TBI offers increased ability to spare organs at risk in pediatric and AYA patients undergoing HSCT, with a favorable acute/subacute toxicity profile and excellent disease control.

View details for DOI 10.1002/pbc.29689

View details for PubMedID 35373904

Abstract

Outcomes for patients with oncologic disease and/or after hematopoietic stem cell transplant (HSCT) requiring intensive care unit admission have improved, but indications for and outcomes after extracorporeal membrane oxygenation (ECMO) support in this population are poorly characterized.We analyzed data from consecutive patients<18 years with oncologic disease and/or after HSCT reported to a pediatric ECMO registry by nine pediatric centers in the United States between 2011 and 2018.We identified 18 ECMO patients with oncologic disease and/or HSCT, and 415 ECMO controls matched with a propensity score algorithm based on age, gender, race, severity of illness at admission, and reason for ECMO. The primary indication for ECMO was respiratory failure in 66.7% in the oncologic disease and/or HSCT group, and in 70.7% in the matched ECMO control group. Eleven of 18 patients survived to hospital discharge (61.1%), similar to the matched control group (60.8%), P=0.979. Children with oncologic disease and/or HSCT had lower mean platelet counts during ECMO and received higher volumes of platelets compared with the control group, mean 14.6mL/kg/day (standard deviations [SD], 9.8) versus mean 9.3mL/kg/day (SD, 10.4), P=0.001. Of the 11 surviving children with oncologic disease and/or HSCT, five sustained new neurologic disorders (45.5%) versus 45 of 222 (20.3%) in the control group, P=0.061. Bleeding complications were similar in the two groups.Outcomes of patients with oncologic disease and/or HSCT supported on ECMO in the current era are not significantly different compared with matched ECMO controls and are improved from previously published reports.

View details for DOI 10.1002/pbc.28403

View details for Web of Science ID 000539018400001

View details for PubMedID 32519430

Abstract

High-risk, recurrent, or refractory solid tumors in pediatric, adolescent, and young adult (AYA) patients have an extremely poor prognosis despite current intensive treatment regimens. We piloted an allogeneic bone marrow transplant platform using reduced-intensity conditioning (RIC) and partially HLA-mismatched (haploidentical) related donors for this population of pediatric and AYA solid tumor patients. Sixteen patients received fludarabine, cyclophosphamide, melphalan, and low-dose total body irradiation RIC haploidentical BMT (haploBMT) followed by post-transplantation cyclophosphamide (PTCy), mycophenolate mofetil, and sirolimus. All assessable patients were full donor chimeras on day 30 with a median neutrophil recovery of 19 days and platelet recovery of 21 days. One patient (7%) exhibited secondary graft failure associated with concomitant infection. The median follow-up time was 15 months. Overall survival was 88%, 56%, and 21% at 6, 12, and 24 months, respectively. Median survival from transplant date was 14 months with a median progression-free survival 7 months. We observed limited graft-versus-host disease in 3 patients and nonrelapse mortality in 1 patient. We demonstrated that RIC haploBMT with PTCy is feasible and has acceptable toxicities in patients with incurable pediatric and AYA solid tumors; thus, this approach serves as a platform for post-transplant strategies to prevent relapse and optimize progression-free survival.

View details for DOI 10.1016/j.bbmt.2017.08.012

View details for Web of Science ID 000418309000016

View details for PubMedID 28807769

View details for PubMedCentralID PMC5986177

Abstract

Viral infections are a leading fatal complication for patients with primary immunodeficiencies (PIDs) who require hematopoietic stem cell transplantation (HSCT). Use of virus-specific T lymphocytes (VSTs) has been successful for the treatment and prevention of viral infections after HSCT for malignant and nonmalignant conditions. Here we describe the clinical use of VSTs in patients with PIDs at 4 centers.We sought to evaluate the safety and efficacy of VSTs for treatment of viral infections in patients with PIDs.Patients with PIDs who have received VST therapy on previous or current protocols were reviewed in aggregate. Clinical information, including transplantation details, viral infections, and use of antiviral and immunosuppressive pharmacotherapy, were evaluated. Data regarding VST production, infusions, and adverse reactions were compared.Thirty-six patients with 12 classes of PID diagnoses received 37 VST products before or after HSCT. Twenty-six (72%) patients had received a diagnosis of infection with cytomegalovirus, EBV, adenovirus, BK virus, and/or human herpesvirus 6. Two patients were treated before HSCT because of EBV-associated lymphoproliferative disease. Partial or complete responses against targeted viruses occurred in 81% of patients overall. Time to response varied from 2weeks to 3months (median, 28days). Overall survival at 6months after therapy was 80%. Four patients had graft-versus-host disease in the 45days after VST infusion, which in most cases was therapy responsive.VSTs derived from either stem cell donors or third-party donors are likely safe and effective for the treatment of viral infections in patients with PIDs.

View details for DOI 10.1016/j.jaci.2015.12.1311

View details for Web of Science ID 000376180200026

View details for PubMedID 26920464

View details for PubMedCentralID PMC4860050

Abstract

Non-infectious lung injury following hematopoietic stem cell transplant may be driven by either immune or non-immune pathways of inflammation. Common alloimmune lung complications include idiopathic pneumonia syndrome (IPS), transfusion related lung injury, diffuse alveolar hemorrhage, and peri-engraftment respiratory distress syndrome, with both diffuse alveolar hemorrhage and peri-engraftment respiratory distress syndrome existing as subsets of IPS when infection is absent. This review will discuss the definitions, risk factors, and pathogeneses of IPS and highlight the diagnostic work-up and novel approaches to treatment.

View details for DOI 10.3233/PIC-14098

View details for Web of Science ID 000218845900007

View details for PubMedID 31214462

View details for PubMedCentralID PMC6530755