Fludarabine-Based Conditioning Chemotherapy for Allogeneic Hematopoietic Stem Cell Transplantation in Acquired Severe Aplastic Anemia

Hazzaa Al-Zahrani, Amr Nassar, Fahad Al-Mohareb, Fahad Al-Sharif, Said Mohamed, Khalid Al-Anazi, Moosa Patel, Walid Rasheed, Abu Jafar Mohammed Saleh, Mahmoud Bakr, Shad Ahmed, Khalid Ibrahim, Fazal Hussain, Naser Elkum, Tusneem Elhassan, Zubeir Nurgat, Naeem Chaudhri, Mahmoud Aljurf

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Thirty-eight patients who met the diagnostic criteria for severe aplastic anemia underwent allogeneic hematopoietic stem cell transplantation (HSCT). The median patient age was 20 years (range, 14-36 years). Twenty-four patients were treatment-naïve, 11 had failed one or more previous courses of immunosuppressive therapy, and 3 had failed a previous HSCT. The conditioning regimen included fludarabine 30 mg/m2/day for 3 days (days -9, -8, and -7) and cyclophosphamide 50 mg/kg/day for 4 days (days -5, -4, -3, and -2). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and short-course methotrexate. All patients underwent transplantation with unmanipulated bone marrow as the stem cell source. The median total nucleated cell (TNC) dose was 2.43 × 108/kg (range, 0.60-6.7 × 108/ kg). The conditioning regimen was well tolerated, with minimal treatment-related mortality. Engraftment was observed in all patients after transplantation; the median time to engraftment of neutrophils and platelets was 18 and 23 days, respectively. Twenty-five of the 27 patients with available chimeric studies at day 180 maintained donor chimerism. Acute GVHD grade ≥II was diagnosed in 4 patients (11%). Extensive chronic GVHD was observed in 8 patients (25%) who survived beyond day +100, at a median observation time of 43 months. Graft rejection with relapse of aplais was observed in one patient. The overall survival (OS) for the whole group was 79%. A trend toward improved OS was observed in the treatment-naïve patients (83% vs 71%), but this was statistically insignificant (P = .384). The fludarabine-based conditioning regimen used in this study with relatively young cohort of patients was well tolerated, with a low rate of rejection and treatment outcomes comparable to those seen in other, more intense and potentially more toxic conditioning regimens. Our results await validation in a larger study, optimally in a randomized controlled manner.

Original languageEnglish
Pages (from-to)717-722
Number of pages6
JournalBiology of Blood and Marrow Transplantation
Volume17
Issue number5
DOIs
Publication statusPublished - May 2011
Externally publishedYes

Fingerprint

Aplastic Anemia
Hematopoietic Stem Cell Transplantation
Drug Therapy
Graft vs Host Disease
fludarabine
Transplantation
Chimerism
Survival
Poisons
Graft Rejection
Therapeutics
Immunosuppressive Agents
Methotrexate
Cyclophosphamide
Cyclosporine
Neutrophils
Stem Cells
Blood Platelets
Bone Marrow
Observation

Keywords

  • Aplastic anemia
  • Fludarabine
  • Transplantation

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

Fludarabine-Based Conditioning Chemotherapy for Allogeneic Hematopoietic Stem Cell Transplantation in Acquired Severe Aplastic Anemia. / Al-Zahrani, Hazzaa; Nassar, Amr; Al-Mohareb, Fahad; Al-Sharif, Fahad; Mohamed, Said; Al-Anazi, Khalid; Patel, Moosa; Rasheed, Walid; Saleh, Abu Jafar Mohammed; Bakr, Mahmoud; Ahmed, Shad; Ibrahim, Khalid; Hussain, Fazal; Elkum, Naser; Elhassan, Tusneem; Nurgat, Zubeir; Chaudhri, Naeem; Aljurf, Mahmoud.

In: Biology of Blood and Marrow Transplantation, Vol. 17, No. 5, 05.2011, p. 717-722.

Research output: Contribution to journalArticle

Al-Zahrani, H, Nassar, A, Al-Mohareb, F, Al-Sharif, F, Mohamed, S, Al-Anazi, K, Patel, M, Rasheed, W, Saleh, AJM, Bakr, M, Ahmed, S, Ibrahim, K, Hussain, F, Elkum, N, Elhassan, T, Nurgat, Z, Chaudhri, N & Aljurf, M 2011, 'Fludarabine-Based Conditioning Chemotherapy for Allogeneic Hematopoietic Stem Cell Transplantation in Acquired Severe Aplastic Anemia', Biology of Blood and Marrow Transplantation, vol. 17, no. 5, pp. 717-722. https://doi.org/10.1016/j.bbmt.2010.08.013
Al-Zahrani, Hazzaa ; Nassar, Amr ; Al-Mohareb, Fahad ; Al-Sharif, Fahad ; Mohamed, Said ; Al-Anazi, Khalid ; Patel, Moosa ; Rasheed, Walid ; Saleh, Abu Jafar Mohammed ; Bakr, Mahmoud ; Ahmed, Shad ; Ibrahim, Khalid ; Hussain, Fazal ; Elkum, Naser ; Elhassan, Tusneem ; Nurgat, Zubeir ; Chaudhri, Naeem ; Aljurf, Mahmoud. / Fludarabine-Based Conditioning Chemotherapy for Allogeneic Hematopoietic Stem Cell Transplantation in Acquired Severe Aplastic Anemia. In: Biology of Blood and Marrow Transplantation. 2011 ; Vol. 17, No. 5. pp. 717-722.
@article{bdaf6ed8d06144708694ae1061f89eb7,
title = "Fludarabine-Based Conditioning Chemotherapy for Allogeneic Hematopoietic Stem Cell Transplantation in Acquired Severe Aplastic Anemia",
abstract = "Thirty-eight patients who met the diagnostic criteria for severe aplastic anemia underwent allogeneic hematopoietic stem cell transplantation (HSCT). The median patient age was 20 years (range, 14-36 years). Twenty-four patients were treatment-na{\"i}ve, 11 had failed one or more previous courses of immunosuppressive therapy, and 3 had failed a previous HSCT. The conditioning regimen included fludarabine 30 mg/m2/day for 3 days (days -9, -8, and -7) and cyclophosphamide 50 mg/kg/day for 4 days (days -5, -4, -3, and -2). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and short-course methotrexate. All patients underwent transplantation with unmanipulated bone marrow as the stem cell source. The median total nucleated cell (TNC) dose was 2.43 × 108/kg (range, 0.60-6.7 × 108/ kg). The conditioning regimen was well tolerated, with minimal treatment-related mortality. Engraftment was observed in all patients after transplantation; the median time to engraftment of neutrophils and platelets was 18 and 23 days, respectively. Twenty-five of the 27 patients with available chimeric studies at day 180 maintained donor chimerism. Acute GVHD grade ≥II was diagnosed in 4 patients (11{\%}). Extensive chronic GVHD was observed in 8 patients (25{\%}) who survived beyond day +100, at a median observation time of 43 months. Graft rejection with relapse of aplais was observed in one patient. The overall survival (OS) for the whole group was 79{\%}. A trend toward improved OS was observed in the treatment-na{\"i}ve patients (83{\%} vs 71{\%}), but this was statistically insignificant (P = .384). The fludarabine-based conditioning regimen used in this study with relatively young cohort of patients was well tolerated, with a low rate of rejection and treatment outcomes comparable to those seen in other, more intense and potentially more toxic conditioning regimens. Our results await validation in a larger study, optimally in a randomized controlled manner.",
keywords = "Aplastic anemia, Fludarabine, Transplantation",
author = "Hazzaa Al-Zahrani and Amr Nassar and Fahad Al-Mohareb and Fahad Al-Sharif and Said Mohamed and Khalid Al-Anazi and Moosa Patel and Walid Rasheed and Saleh, {Abu Jafar Mohammed} and Mahmoud Bakr and Shad Ahmed and Khalid Ibrahim and Fazal Hussain and Naser Elkum and Tusneem Elhassan and Zubeir Nurgat and Naeem Chaudhri and Mahmoud Aljurf",
year = "2011",
month = "5",
doi = "10.1016/j.bbmt.2010.08.013",
language = "English",
volume = "17",
pages = "717--722",
journal = "Biology of Blood and Marrow Transplantation",
issn = "1083-8791",
publisher = "Elsevier Inc.",
number = "5",

}

TY - JOUR

T1 - Fludarabine-Based Conditioning Chemotherapy for Allogeneic Hematopoietic Stem Cell Transplantation in Acquired Severe Aplastic Anemia

AU - Al-Zahrani, Hazzaa

AU - Nassar, Amr

AU - Al-Mohareb, Fahad

AU - Al-Sharif, Fahad

AU - Mohamed, Said

AU - Al-Anazi, Khalid

AU - Patel, Moosa

AU - Rasheed, Walid

AU - Saleh, Abu Jafar Mohammed

AU - Bakr, Mahmoud

AU - Ahmed, Shad

AU - Ibrahim, Khalid

AU - Hussain, Fazal

AU - Elkum, Naser

AU - Elhassan, Tusneem

AU - Nurgat, Zubeir

AU - Chaudhri, Naeem

AU - Aljurf, Mahmoud

PY - 2011/5

Y1 - 2011/5

N2 - Thirty-eight patients who met the diagnostic criteria for severe aplastic anemia underwent allogeneic hematopoietic stem cell transplantation (HSCT). The median patient age was 20 years (range, 14-36 years). Twenty-four patients were treatment-naïve, 11 had failed one or more previous courses of immunosuppressive therapy, and 3 had failed a previous HSCT. The conditioning regimen included fludarabine 30 mg/m2/day for 3 days (days -9, -8, and -7) and cyclophosphamide 50 mg/kg/day for 4 days (days -5, -4, -3, and -2). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and short-course methotrexate. All patients underwent transplantation with unmanipulated bone marrow as the stem cell source. The median total nucleated cell (TNC) dose was 2.43 × 108/kg (range, 0.60-6.7 × 108/ kg). The conditioning regimen was well tolerated, with minimal treatment-related mortality. Engraftment was observed in all patients after transplantation; the median time to engraftment of neutrophils and platelets was 18 and 23 days, respectively. Twenty-five of the 27 patients with available chimeric studies at day 180 maintained donor chimerism. Acute GVHD grade ≥II was diagnosed in 4 patients (11%). Extensive chronic GVHD was observed in 8 patients (25%) who survived beyond day +100, at a median observation time of 43 months. Graft rejection with relapse of aplais was observed in one patient. The overall survival (OS) for the whole group was 79%. A trend toward improved OS was observed in the treatment-naïve patients (83% vs 71%), but this was statistically insignificant (P = .384). The fludarabine-based conditioning regimen used in this study with relatively young cohort of patients was well tolerated, with a low rate of rejection and treatment outcomes comparable to those seen in other, more intense and potentially more toxic conditioning regimens. Our results await validation in a larger study, optimally in a randomized controlled manner.

AB - Thirty-eight patients who met the diagnostic criteria for severe aplastic anemia underwent allogeneic hematopoietic stem cell transplantation (HSCT). The median patient age was 20 years (range, 14-36 years). Twenty-four patients were treatment-naïve, 11 had failed one or more previous courses of immunosuppressive therapy, and 3 had failed a previous HSCT. The conditioning regimen included fludarabine 30 mg/m2/day for 3 days (days -9, -8, and -7) and cyclophosphamide 50 mg/kg/day for 4 days (days -5, -4, -3, and -2). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and short-course methotrexate. All patients underwent transplantation with unmanipulated bone marrow as the stem cell source. The median total nucleated cell (TNC) dose was 2.43 × 108/kg (range, 0.60-6.7 × 108/ kg). The conditioning regimen was well tolerated, with minimal treatment-related mortality. Engraftment was observed in all patients after transplantation; the median time to engraftment of neutrophils and platelets was 18 and 23 days, respectively. Twenty-five of the 27 patients with available chimeric studies at day 180 maintained donor chimerism. Acute GVHD grade ≥II was diagnosed in 4 patients (11%). Extensive chronic GVHD was observed in 8 patients (25%) who survived beyond day +100, at a median observation time of 43 months. Graft rejection with relapse of aplais was observed in one patient. The overall survival (OS) for the whole group was 79%. A trend toward improved OS was observed in the treatment-naïve patients (83% vs 71%), but this was statistically insignificant (P = .384). The fludarabine-based conditioning regimen used in this study with relatively young cohort of patients was well tolerated, with a low rate of rejection and treatment outcomes comparable to those seen in other, more intense and potentially more toxic conditioning regimens. Our results await validation in a larger study, optimally in a randomized controlled manner.

KW - Aplastic anemia

KW - Fludarabine

KW - Transplantation

UR - http://www.scopus.com/inward/record.url?scp=79954627091&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79954627091&partnerID=8YFLogxK

U2 - 10.1016/j.bbmt.2010.08.013

DO - 10.1016/j.bbmt.2010.08.013

M3 - Article

VL - 17

SP - 717

EP - 722

JO - Biology of Blood and Marrow Transplantation

JF - Biology of Blood and Marrow Transplantation

SN - 1083-8791

IS - 5

ER -