Matched sibling donors versus alternative donors in allogeneic hematopoietic stem cell transplantation for pediatric severe aplastic anemia in México Laura Rodríguez 1, Óscar González-Llano 1, Laura Villarreal 1, David Gómez-Almaguer 1, Magdalena Ortiz 2, Alberto Olaya-Vargas 3, Martín Pérez-García3, Guillermo J. Ruíz-Argüelles 4, Guillermo J. Ruíz-Delgado 4, Teodoro Muñiz 5, José De-Diego 6, Nancy Reyes6, Victoria Flores-Villegas 6, Julia Colunga7, Adriana Sandoval8, Óscar González-Ramella 2 Servicio de Hematología del Hospital Universitario “Dr. José E. González”, Universidad Autónoma de Nuevo León (UANL), Monterrey, México, 2Instituto de Investigación en Cáncer Infantil y de la Adolescencia Servicio de Hematología y Oncología, Hospital Civil de Guadalajara “Dr. Juan I. Menchaca”, Guadalajara, Jalisco, México, 3 Servicio de Hematología y Oncología, Instituto Nacional de Pediatría, Secretaría de Salud (SSA), Ciudad de México, México, 4Centro de Hematología y Medicina Interna de Puebla, Clínica Ruíz, Puebla, México, 5Servicio de Hematología y Oncología, Hospital Infantil de México, SSA, Ciudad de México, México, 6Servicio de Hematología, Centro Médico Nacional 20 de Noviembre, ISSSTE, Ciudad de México, México, 7Departamento de Pediatría del Hospital Universitario “Dr. José E. González”, Universidad Autónoma de Nuevo León (UANL), Monterrey, México, 8Servicio de Hematología, UMAE No. 25 IMSS, Monterrey, México 1
Objectives: Hematopoietic stem cell transplantation (HSCT) from a matched sibling donor (MSD) is the preferred initial treatment for children with severe aplastic anemia (SAA). Unfortunately, only about 30% of patients have a suitable human leukocyte antigen-matched sibling. Methods: We have analyzed the outcome of 42 patients who received HSCT (22 MSD and 20 alternative donors (AD)) for SAA at the seven major pediatric HSCT centers in Mexico between 2001 and 2013. Results: With a median follow-up of 30 months (range, 0.4–144), the 5-year overall survival in children transplanted from MSD was 86.4 + 7.3 vs. 49.5 + 11% for children after AD-HSCT (P = 0.013). The cumulative incidence of treatment-related mortality (TRM) was in the MSD-HSCT 9.1 + 3.9% vs. 47.6 + 9.1% in the AD-HSCT context (P = 0.007). Infectious complications contributed to death (91%) of most patients who received AD-HSCT. Discussion: Even when the results of patients given MSD-HSCT are adequate, there is still much room for improvement particularly in children allografted with AD and in the supportive care. The development of an economicwise designed prospective project with MSD or matched unrelated donor HSCTs as a first line of treatment of children with SAA as a unified national trial could address these issues. Keywords: Severe acquired aplastic anemia, Children, Matched sibling donor, Alternative donor, Stem cell transplantation
Introduction Acquired severe aplastic anemia (SAA) is a rare, lifethreatening disorder characterized by pancytopenia and bone marrow (BM) aplasia or hypoplasia.1 Correspondence to: Óscar González-Ramella, Jefe de Unidad de Trasplantes Progenitores Hematopoyéticos Pediátricos, Instituto de Investigación en Cáncer Infantil y de la Adolescencia Servicio de Hematología y Oncología, Hospital Civil de Guadalajara “Dr. Juan I Menchaca”, Salvador Quevedo y Zubieta #550, 44340 Guadalajara, Jalisco, México. Email: [email protected]
© W. S. Maney & Son Ltd 2015 DOI 10.1179/1607845414Y.0000000224
Hematopoietic stem cell transplantation (HSCT) from a matched sibling donor (MSD) is the preferred initial treatment for children with SAA, with longterm survival rates reaching 80–95%.2 Unfortunately, only about 30% of patients have a suitable human leukocyte antigen (HLA)-matched sibling.3Alternative treatment for patients without an MSD is immunosuppressive therapy (IST). Survival rates after IST in children with SAA have been reported to be as high as 80%.4–6 Allogeneic HSCT using alternative donors
Hematology
2015
VOL.
20
NO.
8
449
Rodríguez et al.
Matched sibling donors versus alternative donors in allogeneic hematopoietic stem cell transplantation
(AD) is indicated when patients fail to respond to one or more courses of IST and for patients who experienced disease recurrence after IST.7 The outcome of AD transplantations has been less encouraging, but recent data of patients undergoing AD-HSCT have significantly improved, especially for those who received MUD (matched unrelated donor) HSCT.8–14 We report the results of 42 children with SAA who underwent allogeneic (allo)-HSCT at the seven major pediatric HSCT centers in Mexico, and compare treatment outcomes between MSD vs. AD transplants.
Donors’ characteristics, stem cell source, and dose Among the 42 donors, there were 22 MSD and 20 AD (2 MUD, 15 mismatched unrelated donors (MMUD), 1 mismatched related donor (MMRD) and 2 haploidentical). Of 22 patients transplanted from MSD, 14 received hematopoietic stem cells (HSC) from peripheral blood ( peripheral blood stem cell (PBSC)), and 8 received BM. The source of HSC in AD was umbilical cord blood (UCB) in 17 cases and PBSC in 3 cases. Recipients of HSC from MSD received a median of 4.2 × 106 CD34+ cells/kg (range 1.1–9), while those transplanted from AD obtained a median of 0.36 × 106 CD34+ cells/kg (range 0.25–15.5).
Patients and methods Patients
Conditioning regimens
Data on 42 patients with SAA under the age of 18 years who underwent their first HSCT during 2001–2013 time period were analyzed retrospectively. Patients with congenital BM failure syndrome, such as Fanconi anemia, were excluded from this analysis. Patients’ characteristics are listed in Table 1. Median times from diagnosis to transplantation were 12 months for all patients (range, 1–70 months), 6 months for MSD recipients, and 15 months for AD recipients.
The type of conditioning regimens varied among participating institutions. The majority of MSD-HSCTs, 19 (86%) patients, was conditioning with a reducedintensity regimen. Ten received cyclophosphamide (Cy) and fludarabine, seven received Cy and antithymocyte globulin (ATG), one patient received fludarabine and Cy + ATG, and one patient received only Cy. Three patients among the MSD-HSCTs received myeloablative regimens, two received busulfan and Cy + ATG, and one patient received BuCy. For AD-
Table 1
Patient characteristics Total n (%)
MSD n (%)
AD n (%)
Patients 42 Age (years), median (range) 8 (0.11–17) Female/male 20/22 Prior treatment None 2 ≤2 IST 36 >2 IST 4 Time from diagnosis to transplantation
Objectives: Hematopoietic stem cell transplantation (HSCT) from a matched sibling donor (MSD) is the preferred initial treatment for children with severe aplastic anemia (SAA). Unfortunately, only about 30% of patients have a suitable human leukocyte antigen-matched sibling. Methods: We have analyzed the outcome of 42 patients who received HSCT (22 MSD and 20 alternative donors (AD)) for SAA at the seven major pediatric HSCT centers in Mexico between 2001 and 2013. Results: With a median follow-up of 30 months (range, 0.4–144), the 5-year overall survival in children transplanted from MSD was 86.4 + 7.3 vs. 49.5 + 11% for children after AD-HSCT (P = 0.013). The cumulative incidence of treatment-related mortality (TRM) was in the MSD-HSCT 9.1 + 3.9% vs. 47.6 + 9.1% in the AD-HSCT context (P = 0.007). Infectious complications contributed to death (91%) of most patients who received AD-HSCT. Discussion: Even when the results of patients given MSD-HSCT are adequate, there is still much room for improvement particularly in children allografted with AD and in the supportive care. The development of an economicwise designed prospective project with MSD or matched unrelated donor HSCTs as a first line of treatment of children with SAA as a unified national trial could address these issues. Keywords: Severe acquired aplastic anemia, Children, Matched sibling donor, Alternative donor, Stem cell transplantation
Introduction Acquired severe aplastic anemia (SAA) is a rare, lifethreatening disorder characterized by pancytopenia and bone marrow (BM) aplasia or hypoplasia.1 Correspondence to: Óscar González-Ramella, Jefe de Unidad de Trasplantes Progenitores Hematopoyéticos Pediátricos, Instituto de Investigación en Cáncer Infantil y de la Adolescencia Servicio de Hematología y Oncología, Hospital Civil de Guadalajara “Dr. Juan I Menchaca”, Salvador Quevedo y Zubieta #550, 44340 Guadalajara, Jalisco, México. Email: [email protected]
© W. S. Maney & Son Ltd 2015 DOI 10.1179/1607845414Y.0000000224
Hematopoietic stem cell transplantation (HSCT) from a matched sibling donor (MSD) is the preferred initial treatment for children with SAA, with longterm survival rates reaching 80–95%.2 Unfortunately, only about 30% of patients have a suitable human leukocyte antigen (HLA)-matched sibling.3Alternative treatment for patients without an MSD is immunosuppressive therapy (IST). Survival rates after IST in children with SAA have been reported to be as high as 80%.4–6 Allogeneic HSCT using alternative donors
Hematology
2015
VOL.
20
NO.
8
449
Rodríguez et al.
Matched sibling donors versus alternative donors in allogeneic hematopoietic stem cell transplantation
(AD) is indicated when patients fail to respond to one or more courses of IST and for patients who experienced disease recurrence after IST.7 The outcome of AD transplantations has been less encouraging, but recent data of patients undergoing AD-HSCT have significantly improved, especially for those who received MUD (matched unrelated donor) HSCT.8–14 We report the results of 42 children with SAA who underwent allogeneic (allo)-HSCT at the seven major pediatric HSCT centers in Mexico, and compare treatment outcomes between MSD vs. AD transplants.
Donors’ characteristics, stem cell source, and dose Among the 42 donors, there were 22 MSD and 20 AD (2 MUD, 15 mismatched unrelated donors (MMUD), 1 mismatched related donor (MMRD) and 2 haploidentical). Of 22 patients transplanted from MSD, 14 received hematopoietic stem cells (HSC) from peripheral blood ( peripheral blood stem cell (PBSC)), and 8 received BM. The source of HSC in AD was umbilical cord blood (UCB) in 17 cases and PBSC in 3 cases. Recipients of HSC from MSD received a median of 4.2 × 106 CD34+ cells/kg (range 1.1–9), while those transplanted from AD obtained a median of 0.36 × 106 CD34+ cells/kg (range 0.25–15.5).
Patients and methods Patients
Conditioning regimens
Data on 42 patients with SAA under the age of 18 years who underwent their first HSCT during 2001–2013 time period were analyzed retrospectively. Patients with congenital BM failure syndrome, such as Fanconi anemia, were excluded from this analysis. Patients’ characteristics are listed in Table 1. Median times from diagnosis to transplantation were 12 months for all patients (range, 1–70 months), 6 months for MSD recipients, and 15 months for AD recipients.
The type of conditioning regimens varied among participating institutions. The majority of MSD-HSCTs, 19 (86%) patients, was conditioning with a reducedintensity regimen. Ten received cyclophosphamide (Cy) and fludarabine, seven received Cy and antithymocyte globulin (ATG), one patient received fludarabine and Cy + ATG, and one patient received only Cy. Three patients among the MSD-HSCTs received myeloablative regimens, two received busulfan and Cy + ATG, and one patient received BuCy. For AD-
Table 1
Patient characteristics Total n (%)
MSD n (%)
AD n (%)
Patients 42 Age (years), median (range) 8 (0.11–17) Female/male 20/22 Prior treatment None 2 ≤2 IST 36 >2 IST 4 Time from diagnosis to transplantation
