Alexandra Cheerva

Successful treatment of refractory autoimmune hemolytic anemia with monthly rituximab following nonmyeloablative stem cell transplantation for sickle cell disease.

Autoimmune hemolytic anemia (AIHA) can occur following hematopoietic stem cell transplantation (HSCT) and may be associated with other cytopenias. It can also occur in the context of chronic red cell transfusion in patients maintained on hypertransfusion regimens. There are an increasing number of reports on the successful treatment of autoimmune cytopenias with the monoclonal anti-CD20 antibody rituximab, including a few patients in a post-HSCT setting. The authors report the successful treatment with rituximab of refractory AIHA following allogeneic nonmyeloablative bone marrow transplantation in a child with sickle cell disease.

BK virus-associated hemorrhagic cystitis in pediatric cancer patients receiving high-dose cyclophosphamide.

Hemorrhagic cystitis (HC) is a known complication of oxazophosphorine chemotherapy. BK virus (BKV) has been commonly found to be associated with hematuria in stem cell transplant patients; however, it has rarely been reported after cyclophosphamide chemotherapy alone. The authors present 3 cases of BK viruria with HC in nontransplant pediatric oncology patients. The 3 patients with BKV had more prolonged hematuria (14 to 16 wk) compared with 1 patient with BKV-negative HC (10 wk). The HC necessitated chemotherapy delays and also prolonged supportive care. One patient was treated with intravenous cidofovir with resolution of BK viruria and hematuria. BKV may have an association with the development of HC in nonstem cell transplant patients receiving high-dose oxazophosphorine chemotherapy. HC may present early and be more prolonged in patients with BK viruria. Patients with HC after cyclophosphamide or ifosfamide with negative bacterial cultures should be studied for BKV. Cidofovir may be beneficial in certain patients with BK viruria and HC; however, definitive data will require a clinical trial.

Pre‐stem cell transplantation enzyme replacement therapy in Hurler syndrome does not lead to significant antibody formation or delayed recovery of the endogenous enzyme post‐transplant: A case report

Abstract:  Combined enzyme replacement therapy (ERT) and stem cell transplant (SCT) were done for a two year old boy with severe Hurler syndrome(HS) with the aim to decrease transplant related complications. He tolerated both the procedures well without any major complications. Urine glycosaminoglycans (GAGs) decreased post‐transplant and child has improved clinically and neurologically. Insignificant titers of the anti‐iduronidase antibodies which developed post‐transplant did not affect the transplant outcome or the endogenous recovery of the alpha‐L‐iduronidase enzyme.

Successful unrelated umbilical cord blood transplantation for class 3 β-thalassemia major using a reduced-toxicity regimen.

Unrelated umbilical CB transplant for class 3 β‐thalassemia major is associated with an increased risk of mortality and non‐engraftment. We describe two patients who underwent successful unrelated umbilical CB transplant using a novel reduced‐toxicity preparative regimen. This regimen may be sufficiently immunosuppressive and myeloablative to ensure engraftment with reduced risks of toxicity and mortality. Close monitoring of HHV‐6 viral load is advised for patients undergoing transplant with this regimen.

Cerebral toxoplasmosis after tandem high-dose chemotherapy and autologous hematopoietic cell transplant for neuroblastoma.

Toxoplasmosis is a well-recognized life-threatening complication of hematopoietic cell transplantation (HCT). This report describes a pediatric patient with stage 4 neuroblastoma who developed cerebral toxoplasmosis after tandem high-dose chemotherapy with autologous HCT. Toxoplasmosis is rare in patients undergoing autologous HCT; however, tandem autologous HCT is more immunosuppressive than a single autologous HCT. Toxoplasmosis is a potential complication in autologous as well as allogeneic transplants, and should be considered in any post-HCT patient with neurological dysfunction. Rapid diagnosis and immediate antimicrobial treatment are crucial to avoid morbidity and mortality. Evaluation of toxoplasma serology should be standard in all patients undergoing tandem autologous HCT and seropositive patients should be started on appropriate prophylactic therapy.

Extracorporeal photopheresis for the treatment of severe, refractory steroid dependent pediatric Crohn's Disease

Crohns disease is a chronic, inflammatory disease of the gastrointestinal tract, affecting both children and adults. Extracorporeal photopheresis (ECP) has been used in steroid dependent adults with moderate to severely active Crohns disease, with response rates up to 50%, with up to 25% complete responses. A 12‐year‐old male patient had severe unremitting Crohns disease for one year, despite treatment with anti‐inflammatory, immunosuppressive, and biologic agents. He failed elemental enteral nutrition and required total parenteral nutrition (TPN). A diverting colostomy for perforation was required. He required frequent hospitalizations and required homebound schooling. Endoscopy revealed severe inflammation and ulcerations of the entire colon. ECP was begun twice weekly for 4 weeks, then twice per week every 14 days for a total of 28 weeks. ECP was well tolerated and prednisone was gradually discontinued. He continued daily azathioprine and infliximab at 6 week intervals. TPN was weaned as enteral intake improved. Disease abatement allowed a return to school and normal activities. Endoscopy at completion of ECP course revealed normal upper tract, normal ano‐rectum, and decreased, although significant, colonic disease. This response has continued for at least 16 months since completion of ECP. We conclude that ECP is useful for pediatric patients with steroid dependent Crohns disease and prospective evaluation is warranted. J. Clin. Apheresis 28:381–386, 2013.

The safety and efficacy of clofarabine in combination with high-dose cytarabine and total body irradiation myeloablative conditioning and allogeneic stem cell transplantation in children, adolescents, and young adults (CAYA) with poor-risk acute leukemia

Acute leukemias in children with CR3, refractory relapse, or induction failure (IF) have a poor prognosis. Clofarabine has single agent activity in relapsed leukemia and synergy with cytarabine. We sought to determine the safety and overall survival in a Phase I/II trial of conditioning with clofarabine (doses 40 – 52 mg/m2), cytarabine 1000 mg/m2, and 1200 cGy TBI followed by alloSCT in children, adolescents, and young adults with poor-risk leukemia. Thirty-seven patients; Age 12 years (1–22 years); ALL/AML: 34:3 (18 IF, 10 CR3, 13 refractory relapse); 15 related, 22 unrelated donors. Probabilities of neutrophil, platelet engraftment, acute GvHD, and chronic GvHD were 94%, 84%, 49%, and 30%, respectively. Probability of day 100 TRM was 8.1%. 2-year EFS (event free survival) and OS (overall survival) were 38.6% (CI95: 23–54%), and 41.3% (CI95: 25–57%). Multivariate analysis demonstrated overt disease at time of transplant (relative risk (RR) 3.65, CI95: 1.35–9.89, P = 0.011) and umbilical cord blood source (RR 2.17, CI95: 1.33–4.15, P = 0.019) to be predictors of worse EFS/OS. This novel myeloablative conditioning regimen followed by alloSCT is safe and well tolerated in CAYA with very poor-risk ALL or AML. Further investigation in CAYA with better risk ALL and AML undergoing alloSCT is warranted.

Cytomegalovirus Treatment in Pediatric Hematopoietic Stem Cell Transplant Patients.

Cytomegalovirus (CMV) is a frequent complication of hematopoietic stem cell transplant in pediatric patients, with significant morbidity and mortality. Antiviral drugs are used as prophylactic, preemptive or therapeutic medicines; however, no uniform guidelines exist for the best strategy to prevent CMV disease. Resistance to standard antiviral therapies can lead to further difficulty in managing CMV disease. Studies for investigational therapies are underway and could provide options for treatment of resistant CMV, while limiting toxicities associated with currently used antiviral therapies.

Stereotactic Ablative Radiotherapy for a Lung Metastasis in a Child With Ewing's Sarcoma.

Stereotactic ablative radiotherapy delivers a high dose of radiation to a small volume over several fractions. Although most commonly used as a treatment alternative to surgery in adult patients with primary lung cancer, its use has now been reported in children with metastatic disease to the lungs. We present the case of a child treated with stereotactic ablative radiotherapy to pulmonary metastases in preparation for a salvage stem cell transplant. The patient was treated to a dominant pulmonary nodule and successfully received his stem cell transplant, however he developed clinical and radiographic findings consistent with pneumonitis several months after treatment.