Unrelated Donor Cord Blood Transplantation for Children with Severe Sickle Cell Disease

Results of One Cohort from the Phase II Study from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN)

Naynesh R. Kamani, Mark C. Walters, Shelly Carter, Victor Aquino, Joel A. Brochstein, Sonali Chaudhury, Mary Eapen, Brian M. Freed, Michael Grimley, John E. Levine, Brent Logan, Theodore Moore, Julie Panepinto, Suhag Parikh, Michael A. Pulsipher, Jane Sande, Kirk R. Schultz, Stephen Spellman, Shalini Shenoy

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1265-1272
Number of pages8
JournalBiology of Blood and Marrow Transplantation
Volume18
Issue number8
DOIs
StatePublished - Aug 2012

Fingerprint

Unrelated Donors
Sickle Cell Anemia
Fetal Blood
Transplantation
Bone Marrow
Clinical Trials
Transplants
Graft vs Host Disease
Neutrophils
Tissue Donors
Mycophenolic Acid
Molecular Typing
Melphalan
HLA-A Antigens
HLA-B Antigens
Cell Transplantation
Graft Rejection
Tacrolimus
Respiratory Insufficiency
Cyclosporine

Keywords

  • Children
  • Cord blood
  • Sickle cell disease
  • Transplantation
  • Unrelated donor

ASJC Scopus subject areas

  • Transplantation
  • Hematology

Cite this

Unrelated Donor Cord Blood Transplantation for Children with Severe Sickle Cell Disease : Results of One Cohort from the Phase II Study from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN). / Kamani, Naynesh R.; Walters, Mark C.; Carter, Shelly; Aquino, Victor; Brochstein, Joel A.; Chaudhury, Sonali; Eapen, Mary; Freed, Brian M.; Grimley, Michael; Levine, John E.; Logan, Brent; Moore, Theodore; Panepinto, Julie; Parikh, Suhag; Pulsipher, Michael A.; Sande, Jane; Schultz, Kirk R.; Spellman, Stephen; Shenoy, Shalini.

In: Biology of Blood and Marrow Transplantation, Vol. 18, No. 8, 08.2012, p. 1265-1272.

Research output: Contribution to journalArticle

Kamani, NR, Walters, MC, Carter, S, Aquino, V, Brochstein, JA, Chaudhury, S, Eapen, M, Freed, BM, Grimley, M, Levine, JE, Logan, B, Moore, T, Panepinto, J, Parikh, S, Pulsipher, MA, Sande, J, Schultz, KR, Spellman, S & Shenoy, S 2012, 'Unrelated Donor Cord Blood Transplantation for Children with Severe Sickle Cell Disease: Results of One Cohort from the Phase II Study from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN)', Biology of Blood and Marrow Transplantation, vol. 18, no. 8, pp. 1265-1272. https://doi.org/10.1016/j.bbmt.2012.01.019
Kamani, Naynesh R. ; Walters, Mark C. ; Carter, Shelly ; Aquino, Victor ; Brochstein, Joel A. ; Chaudhury, Sonali ; Eapen, Mary ; Freed, Brian M. ; Grimley, Michael ; Levine, John E. ; Logan, Brent ; Moore, Theodore ; Panepinto, Julie ; Parikh, Suhag ; Pulsipher, Michael A. ; Sande, Jane ; Schultz, Kirk R. ; Spellman, Stephen ; Shenoy, Shalini. / Unrelated Donor Cord Blood Transplantation for Children with Severe Sickle Cell Disease : Results of One Cohort from the Phase II Study from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN). In: Biology of Blood and Marrow Transplantation. 2012 ; Vol. 18, No. 8. pp. 1265-1272.
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abstract = "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.",
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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.

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AU - Schultz, Kirk R.

AU - Spellman, Stephen

AU - Shenoy, Shalini

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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.

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KW - Children

KW - Cord blood

KW - Sickle cell disease

KW - Transplantation

KW - Unrelated donor

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