TY - JOUR
T1 - Unrelated Donor Cord Blood Transplantation for Children with Severe Sickle Cell Disease
T2 - Results of One Cohort from the Phase II Study from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN)
AU - Kamani, Naynesh R.
AU - Walters, Mark C.
AU - Carter, Shelly
AU - Aquino, Victor
AU - Brochstein, Joel A.
AU - Chaudhury, Sonali
AU - Eapen, Mary
AU - Freed, Brian M.
AU - Grimley, Michael
AU - Levine, John E.
AU - Logan, Brent
AU - Moore, Theodore
AU - Panepinto, Julie
AU - Parikh, Suhag
AU - Pulsipher, Michael A.
AU - Sande, Jane
AU - Schultz, Kirk R.
AU - Spellman, Stephen
AU - Shenoy, Shalini
N1 - Funding Information:
Financial disclosure: This BMT CTN trial is supported in part by grant #U01HL069294 from the National Heart, Lung, and Blood Institute and the National Cancer Institute , and by the National Marrow Donor Program , NIH's National Center of Minority Health and Health Disparities, and the NHLBI's Sickle Cell Disease Clinical Research Network.
PY - 2012/8
Y1 - 2012/8
N2 - The Sickle Cell Unrelated Donor Transplant Trial (SCURT trial) of the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) is a phase II study of the toxicity and efficacy of unrelated donor hematopoietic cell transplantation in children with severe sickle cell disease (SCD) using a reduced-intensity conditioning regimen. Here we report the results for the cord blood cohort of this trial. Eight children with severe SCD underwent unrelated donor cord blood transplantation (CBT) following alemtuzumab, fludarabine, and melphalan. Cyclosporine or tacrolimus and mycophenolate mofetil were administered for graft-versus-host disease (GVHD) prophylaxis. Donor/recipient HLA match status was 6 of 6 (n = 1) or 5 of 6 (n = 7), based on low/intermediate-resolution molecular typing at HLA -A, -B, and high-resolution typing at -DRB1. Median recipient age was 13.7 years (range: 7.4-16.2 years), and median weight was 35.0 kg (range: 25.2-90.2 kg). The median precryopreservation total nucleated cell dose was 6.4 × 107 /kg (range: 3.1-7.6), and the median postthaw infused CD34 cell dose was 1.5 × 105 /kg (range: 0.2-2.3). All patients achieved neutrophil recovery (absolute neutrophil count >500/mm3) by day 33 (median: 22 days). Three patients who engrafted had 100% donor cells by day 100, which was sustained, and 5 patients had autologous hematopoietic recovery. Six of 8 patients had a platelet recovery to >50,000/mm3 by day 100. Two patients developed grade II acute GVHD. Of these, 1 developed extensive chronic GVHD and died of respiratory failure 14 months posttransplantation. With a median follow-up of 1.8 years (range: 1-2.6), 7 patients are alive with a 1-year survival of 100%, and 3 of 8 are alive without graft failure or disease recurrence. Based upon the high incidence of graft rejection after unrelated donor CBT, enrollment onto the cord blood arm of the SCURT trial was suspended. However, because this reduced-intensity regimen has demonstrated a favorable safety profile, this trial remains open to enrollment for unrelated marrow donor transplants. Novel approaches aimed at improving engraftment will be needed before unrelated CBT can be widely adopted for transplanting patients with severe SCD.
AB - The Sickle Cell Unrelated Donor Transplant Trial (SCURT trial) of the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) is a phase II study of the toxicity and efficacy of unrelated donor hematopoietic cell transplantation in children with severe sickle cell disease (SCD) using a reduced-intensity conditioning regimen. Here we report the results for the cord blood cohort of this trial. Eight children with severe SCD underwent unrelated donor cord blood transplantation (CBT) following alemtuzumab, fludarabine, and melphalan. Cyclosporine or tacrolimus and mycophenolate mofetil were administered for graft-versus-host disease (GVHD) prophylaxis. Donor/recipient HLA match status was 6 of 6 (n = 1) or 5 of 6 (n = 7), based on low/intermediate-resolution molecular typing at HLA -A, -B, and high-resolution typing at -DRB1. Median recipient age was 13.7 years (range: 7.4-16.2 years), and median weight was 35.0 kg (range: 25.2-90.2 kg). The median precryopreservation total nucleated cell dose was 6.4 × 107 /kg (range: 3.1-7.6), and the median postthaw infused CD34 cell dose was 1.5 × 105 /kg (range: 0.2-2.3). All patients achieved neutrophil recovery (absolute neutrophil count >500/mm3) by day 33 (median: 22 days). Three patients who engrafted had 100% donor cells by day 100, which was sustained, and 5 patients had autologous hematopoietic recovery. Six of 8 patients had a platelet recovery to >50,000/mm3 by day 100. Two patients developed grade II acute GVHD. Of these, 1 developed extensive chronic GVHD and died of respiratory failure 14 months posttransplantation. With a median follow-up of 1.8 years (range: 1-2.6), 7 patients are alive with a 1-year survival of 100%, and 3 of 8 are alive without graft failure or disease recurrence. Based upon the high incidence of graft rejection after unrelated donor CBT, enrollment onto the cord blood arm of the SCURT trial was suspended. However, because this reduced-intensity regimen has demonstrated a favorable safety profile, this trial remains open to enrollment for unrelated marrow donor transplants. Novel approaches aimed at improving engraftment will be needed before unrelated CBT can be widely adopted for transplanting patients with severe SCD.
KW - Children
KW - Cord blood
KW - Sickle cell disease
KW - Transplantation
KW - Unrelated donor
UR - http://www.scopus.com/inward/record.url?scp=84864005843&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84864005843&partnerID=8YFLogxK
U2 - 10.1016/j.bbmt.2012.01.019
DO - 10.1016/j.bbmt.2012.01.019
M3 - Article
C2 - 22343376
AN - SCOPUS:84864005843
SN - 1083-8791
VL - 18
SP - 1265
EP - 1272
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 8
ER -