Martin Andreansky

Successful Matched Sibling Donor Marrow Transplantation Following Reduced Intensity Conditioning in Children with Hemoglobinopathies

Fifty‐two children with symptomatic sickle cell disease sickle cell disease (SCD) (N = 43) or transfusion‐dependent thalassemia (N = 9) received matched sibling donor marrow (46), marrow and cord product (5), or cord blood (1) allografts following reduced intensity conditioning (RIC) with alemtuzumab, fludarabine, and melphalan between March 2003 and May 2014*. The Kaplan–Meier probabilities of overall and event‐free survival at a median of 3.42 (range, 0.75–11.83) years were 94.2% and 92.3% for the group, 93% and 90.7% for SCD, and 100% and 100% for thalassemia, respectively. Treatment‐related mortality (all related to graft versus host disease, GVHD) was noted in three (5.7%) recipients, all 17–18 years of age. Acute and chronic GVHD was noted in 23% and 13%, respectively, with 81% of recipients off immunosuppression by 1 year. Graft rejection was limited to the single umbilical cord blood recipient who had prompt autologous hematopoietic recovery. Fourteen (27%) had mixed chimerism at 1 year and beyond; all had discontinued immunosuppression between 4 and 12 months from transplant with no subsequent consequence on GVHD or rejection. Infectious complications included predominantly bacteremia (48% were staphylococcus) and CMV reactivation (43%) necessitating preemptive therapy. Lymphocyte recovery beyond 6 months was associated with subsidence of infectious complications. All patients who engrafted were transfusion independent; no strokes or pulmonary complications of SCD were noted, and pain symptoms subsided within 6 months posttransplant. These findings support using RIC for patients with hemoglobinopathy undergoing matched sibling marrow transplantation (*www.Clinical Trials.gov: NCT00920972, NCT01050855, NCT02435901). Am. J. Hematol. 90:1093–1098, 2015.

Outcomes after Hematopoietic Stem Cell Transplantation for Children with I-Cell Disease

Mucolipidosis type II (MLII), or I-cell disease, is a rare but severe disorder affecting localization of enzymes to the lysosome, generally resulting in death before the 10th birthday. Although hematopoietic stem cell transplantation (HSCT) has been used to successfully treat some lysosomal storage diseases, only 2 cases have been reported on the use of HSCT to treat MLII. For the first time, we describe the combined international experience in the use of HSCT for MLII in 22 patients. Although 95% of the patients engrafted, overall survival was low, with only 6 patients (27%) alive at last follow-up. The most common cause of death post-transplant was cardiovascular complications, most likely due to disease progression. Survivors were globally delayed in development and often required complex medical support, such as gastrostomy tubes for nutrition and tracheostomy with mechanical ventilation. Although HSCT has demonstrated efficacy in treating some lysosomal storage disorders, the neurologic outcome and survival for patents with MLII were poor. Therefore, new medical and cellular therapies should be sought for these patients.

Unrelated Donor Transplantation in Children with Thalassemia using Reduced-Intensity Conditioning: The URTH Trial

Allogeneic hematopoietic stem cell transplantation (HSCT) can cure transfusion-dependent thalassemia (TDT). In a multicenter trial we investigated the efficacy of reduced-intensity conditioning (RIC) before unrelated donor (URD) HSCT in children with TDT. Thirty-three children, ages 1 to 17 years, received bone marrow (BM) or umbilical cord blood (UCB) allografts. Median time to neutrophil engraftment was 13 days (range, 10 to 25) and 24 days (range, 18 to 49) and platelet engraftment 23 days (range, 12 to 46) and 50 days (range, 31 to 234) after BM and UCB allografts, respectively. With a median follow-up of 58 months (range, 7 to 79), overall and thalassemia-free survival was 82% (95% CI, .64% to .92%) and 79% (95% CI, .6% to .9%), respectively. The cumulative incidence of grades II to IV acute graft-versus-host disease (GVHD) after BM and UCB allografts was 24% and 44%; the 2-year cumulative incidence of chronic extensive GVHD was 29% and 21%, respectively; 71% of BM and 91% of UCB recipients discontinued systemic immunosuppression by 2 years. Six patients who had Pesaro risk class 2 (n = 5) and class 3 (n = 1) died of GVHD (n = 3), viral pneumonitis (n = 2) and pulmonary hemorrhage (n = 1). Outcomes after this RIC compared favorably with URD HSCT outcomes for TDT and supported engraftment in 32 of 33 patients. Efforts to reduce GVHD and infectious complications are being pursued further.

Intra-Arterial Platelet Infusion for Intractable Hemorrhage and Refractory

Acute gastrointestinal graft‐versus‐host disease (GVHD) refractory to first‐line treatment with systemic corticosteroids results in increased morbidity and potential mortality. We retrospectively assessed the feasibility and efficacy of catheter‐directed intra‐arterial platelet infusion (IAPI) in two pediatric patients with steroid and transfusion refractory gastrointestinal GVHD causing intractable lower gastrointestinal hemorrhage and refractory thrombocytopenia, that were referred for salvage therapy. Immediate angiographic response was noted with a resolution of hemorrhage and decreased blood requirements. We reviewed the literature regarding this treatment modality and compared it to the available minimally invasive transcatheter techniques to control gastrointestinal hemorrhage. Pediatr Blood Cancer

Intra-Arterial Platelet Infusion for Intractable Hemorrhage and Refractory: Intra-Arterial Platelet Infusion in GVHD

Acute gastrointestinal graft‐versus‐host disease (GVHD) refractory to first‐line treatment with systemic corticosteroids results in increased morbidity and potential mortality. We retrospectively assessed the feasibility and efficacy of catheter‐directed intra‐arterial platelet infusion (IAPI) in two pediatric patients with steroid and transfusion refractory gastrointestinal GVHD causing intractable lower gastrointestinal hemorrhage and refractory thrombocytopenia, that were referred for salvage therapy. Immediate angiographic response was noted with a resolution of hemorrhage and decreased blood requirements. We reviewed the literature regarding this treatment modality and compared it to the available minimally invasive transcatheter techniques to control gastrointestinal hemorrhage. Pediatr Blood Cancer

Intra-Arterial Platelet Infusion for Intractable Hemorrhage and Refractory Thrombocytopenia in Children With Gastrointestinal Graft-Versus-Host Disease.

Acute gastrointestinal graft‐versus‐host disease (GVHD) refractory to first‐line treatment with systemic corticosteroids results in increased morbidity and potential mortality. We retrospectively assessed the feasibility and efficacy of catheter‐directed intra‐arterial platelet infusion (IAPI) in two pediatric patients with steroid and transfusion refractory gastrointestinal GVHD causing intractable lower gastrointestinal hemorrhage and refractory thrombocytopenia, that were referred for salvage therapy. Immediate angiographic response was noted with a resolution of hemorrhage and decreased blood requirements. We reviewed the literature regarding this treatment modality and compared it to the available minimally invasive transcatheter techniques to control gastrointestinal hemorrhage. Pediatr Blood Cancer