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Adult Umbilical Cord Blood Transplantation Following Non-Myeloablative Conditioning; Impact of Increased Cell Dose and 200cGy TBI on Engraftment and Survival.

Publication ,  Conference
Horwitz, M; Rizzieri, D; Long, GD; Gasparetto, C; Morris, A; Sullivan, K; Chute, J; Marshall, D; Chao, N
Published in: Blood
November 16, 2006

Reliable engraftment following transplantation of partially matched umbilical cord blood is dependent upon adequate immunosuppression and myelosuppression. The lowest intensity conditioning regimen that will provide reliable cord blood engraftment in adult patients has not been determined. 26 adult patients with a contraindication for myeloablative marrow conditioning due to advanced age or comorbidities, underwent non-myeloablative umbilical cord blood transplantation for hematologic malignancies. The first 13 patients (Cohort 1) were conditioned with Fludarabine 120mg/m2, Cyclophosphamide 2g/m2 and horse Antithymocyte globulin 90mg/kg. Cyclosporine and Mycophenolate Mofetil was administered for GvHD prophylaxis. The median cell nucleated dose was 2.1 × 107/kg and median follow-up is 60 months (Chao 2004 BBMT 10:569). After protocol revision, 200 cGy total body irradiation was added to the regimen described above. In addition, the minimum nucleated cell dose provided from up to two cord blood units was increased to 3 × 107/kg (Cohort 2). With a median follow-up of 12 months, we now report the outcome of cohort 2. Fourteen patients with AML CR1 (2), CR≥2 (5), CML (1), MDS/AML (1), MDS (4), or Follicular Lymphoma (1) and a median age of 54 (range 21–72) were transplanted. Eight patients required dual cord blood grafts to achieve the minimum cell dose. All grafts were at least 4/6 HLA matches (antigen level class I, allele level class II) with the patient, and with each other (dual cord blood grafts). The median cryopreserved and infused nucleated cell dose was 3.6 × 107/kg and 3.5 × 107/kg respectively. Two patients were not evaluable for engraftment due to early toxic death. Two patients experienced primary graft failure. Acute GvHD (grade II skin) was observed in 2 patients. Limited chronic GvHD developed in 2 patients. Parainfluenza type 3 sinusitis and pneumonitis caused significant morbidity in 5 patients. Day 100 treatment-related mortality occurred in 4 patients (30%) due to; infection (2), hemorrhage (2). Relapse occurred in 5 patients (36%). The estimated one year overall and disease-free survival is 25% and 17%, respectively. T-cell recovery was slow. The median CD4 count/ul for engrafted patients was 44 (range 4–516) and 61(range 2–237) at 3 and 6 months following transplantation, respectively. The median CD8 count/ul was 7 (range 0–359) and 108 (range 0–728) at 3 and 6 months following transplantation, respectively. A comparison of results from the two cohorts is presented in the table. The addition of 200cGy and increasing the cell dose facilitated by dual cord blood transplantation doubled the chance for sustained donor engraftment. Improved engraftment was accompanied by increased treatment-related morbidity and mortality, erasing the potential for improved disease-free survival. Disease relapse, in part due to slow immune recovery resulting in impaired anti-tumor response, was the other major impediment to successful outcome. Techniques focused on enhancing immune recovery would significantly improve outcomes of adult cord blood transplantation.Comparison of Cohort 1 vs Cohort 2 Evaluable Patients Med. Nuc Cell Dose/kg D100 TRM(%) Sustained Donor Engraftment (%)† Disease-Free Survival(%)† †estimated (1yr) *P=0.08 **P=NS Flu / Cy / ATG (Cohort 1) 13 2.1 × 107 15 41 15 Flu/Cy/ATG/200cGy(Cohort 2) 12 3.5 × 107 30 83* 17**

Duke Scholars

Published In

Blood

DOI

EISSN

1528-0020

ISSN

0006-4971

Publication Date

November 16, 2006

Volume

108

Issue

11

Start / End Page

5399 / 5399

Publisher

American Society of Hematology

Related Subject Headings

  • Immunology
  • 3213 Paediatrics
  • 3201 Cardiovascular medicine and haematology
  • 3101 Biochemistry and cell biology
  • 1114 Paediatrics and Reproductive Medicine
  • 1103 Clinical Sciences
  • 1102 Cardiorespiratory Medicine and Haematology
 

Citation

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Horwitz, M., Rizzieri, D., Long, G. D., Gasparetto, C., Morris, A., Sullivan, K., … Chao, N. (2006). Adult Umbilical Cord Blood Transplantation Following Non-Myeloablative Conditioning; Impact of Increased Cell Dose and 200cGy TBI on Engraftment and Survival. In Blood (Vol. 108, pp. 5399–5399). American Society of Hematology. https://doi.org/10.1182/blood.v108.11.5399.5399
Horwitz, Mitchell, David Rizzieri, Gwynn D. Long, Cristina Gasparetto, Ashley Morris, Keith Sullivan, John Chute, Dawn Marshall, and Nelson Chao. “Adult Umbilical Cord Blood Transplantation Following Non-Myeloablative Conditioning; Impact of Increased Cell Dose and 200cGy TBI on Engraftment and Survival.” In Blood, 108:5399–5399. American Society of Hematology, 2006. https://doi.org/10.1182/blood.v108.11.5399.5399.
Horwitz M, Rizzieri D, Long GD, Gasparetto C, Morris A, Sullivan K, et al. Adult Umbilical Cord Blood Transplantation Following Non-Myeloablative Conditioning; Impact of Increased Cell Dose and 200cGy TBI on Engraftment and Survival. In: Blood. American Society of Hematology; 2006. p. 5399–5399.
Horwitz, Mitchell, et al. “Adult Umbilical Cord Blood Transplantation Following Non-Myeloablative Conditioning; Impact of Increased Cell Dose and 200cGy TBI on Engraftment and Survival.Blood, vol. 108, no. 11, American Society of Hematology, 2006, pp. 5399–5399. Crossref, doi:10.1182/blood.v108.11.5399.5399.
Horwitz M, Rizzieri D, Long GD, Gasparetto C, Morris A, Sullivan K, Chute J, Marshall D, Chao N. Adult Umbilical Cord Blood Transplantation Following Non-Myeloablative Conditioning; Impact of Increased Cell Dose and 200cGy TBI on Engraftment and Survival. Blood. American Society of Hematology; 2006. p. 5399–5399.

Published In

Blood

DOI

EISSN

1528-0020

ISSN

0006-4971

Publication Date

November 16, 2006

Volume

108

Issue

11

Start / End Page

5399 / 5399

Publisher

American Society of Hematology

Related Subject Headings

  • Immunology
  • 3213 Paediatrics
  • 3201 Cardiovascular medicine and haematology
  • 3101 Biochemistry and cell biology
  • 1114 Paediatrics and Reproductive Medicine
  • 1103 Clinical Sciences
  • 1102 Cardiorespiratory Medicine and Haematology