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The Effect of Bone Marrow Graft Composition on Pediatric Bone Marrow Transplantation Outcomes
Abstracts / Biol Blood Marrow Transplant 22 (2016) S19eS481
empiric coverage in 60% of ST-related fevers, while in other 40% of cases, a different antibiotic(s) was used. The median length of antibiotic therapy was 72 hours (range 24-120) in 39 (66%) patients whose antibiotics were discontinued upon resolution of ST-related symptoms. In 20 (34%) patients, antibiotics were continued until resolution of neutropenia. Table 1 summarizes documented episodes of BSI during HCT using CDC/NHSN criteria. There were no episodes of gramnegative BSI during ST. Among 4 BSI during ST, only 1 (Coagulase negative staphylococci) occurred in a patient with ANC >500 at the start of ST. In patients with ANC>500 at the start of ST and a new fever, the risk of BSI is low (1/45; 2.2%; 95% CI 0.05-12%). Although fever resolved within 48 hours in 80% of patients, 82% of patients received >48 hours of empiric antibiotic therapy, due to the wait for negative culture results and extension of therapy in patients who became neutropenic during serotherapy. Prospective studies should address whether observation without antibiotics or use of shorter antibiotic courses is safe in children with ST-related fever and ANC>500.
349 Relationship of ABO Incompatible HSCT to Outcomes in Pediatric Patients Laura Jenkins 1, Elizabeth Garrett-Mayer 2, Elizabeth J. Williams 3, Elsie Hill 1, Cindy Kramer 3, Stacey Warneke 3, Jennifer Joi Jaroscak 4, Michelle Hudspeth 4. 1 Medical University of South Carolina, Charleston, SC; 2 Biostatistics, Medical University of South Carolina, Charleston, SC; 3 Blood and Marrow Transplant Program, Medical University of South Carolina, Charleston, SC; 4 Pediatric Hematology/Oncology, Medical University of South Carolina, Charleston, SC Minimal data exist regarding the impact of ABO incompatible transplants on outcomes of pediatric HSCT. We sought to determine the influence of ABO incompatibility on several outcomes in pediatric HSCT. We conducted a retrospective chart review of pediatric patients undergoing HSCT at our institution from 7/1/2007 to 7/1/2014 with at least 1 year of follow-up post-transplant. Four patients were excluded from the study, including two recipients of double cord blood transplants and two recipients of Rh incompatible transplants. Fisher’s exact test was used to compare baseline characteristics of the two groups. Median number of RBC and platelet transfusions were compared using the Wilcoxon rank sum test. Kaplan-Meier estimates were used to generate time to neutrophil engraftment and survival curves that were compared by the log-rank test. 38 patients received ABO compatible transplants, and 47 patients received ABO incompatible transplants within our time period. There was no statistically significant difference between the ABO compatible group and the ABO incompatible group with regards to diagnosis, preparative regimen, graft source, or degree of HLA match. 18 of the 47 patients (38%) who underwent ABO incompatible transplants switched to donor blood type within our follow-up period. Median time to neutrophil engraftment was 17 days for both groups. The median number of RBC and platelet transfusions required in the first 100 days following transplant did not significantly differ between the ABO compatible group (5.5 and 16) and the ABO incompatible group (8 and 13), p-values 0.54 and 0.59, respectively. The median survival, 2 year survival, and 5 year survival were not statistically significant between the ABO compatible
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group (3.21 yrs, 51%, and 46%) and the ABO incompatible group (5.64 yrs, 57%, and 54% ) with a p-value of 0.74. ABO incompatibility does not appear to affect neutrophil engraftment, early transfusion needs, or survival in pediatric HSCT. Findings should be validated in larger multiinstitution pediatric studies.
350 The Effect of Bone Marrow Graft Composition on Pediatric Bone Marrow Transplantation Outcomes Vanessa Fabrizio 1, Amy Wahlquist 2, Elsie Hill 1, Elizabeth J. Williams 3, Cindy Kramer 3, Jennifer Joi Jaroscak 4, Elizabeth Garrett-Mayer 2, Michelle Hudspeth 4. 1 Medical University of South Carolina, Charleston, SC; 2 Biostatistics, Medical University of South Carolina, Charleston, SC; 3 Blood and Marrow Transplant Program, Medical University of South Carolina, Charleston, SC; 4 Pediatric Hematology/Oncology, Medical University of South Carolina, Charleston, SC The cellular composition of the hematopoietic stem cell graft has generally been accepted to have an impact on transplantation outcomes. Recent studies have questioned this hypothesis for bone marrow grafts. A NMDP and CIBMTR study published in 2010 demonstrated a lack of effect of the composition of unrelated bone marrow donor grafts on outcomes but only included 44 pediatric recipients. We sought to determine if the infused TNC, CD34+ cell count, and CD3+ cell count had effects on neutrophil engraftment, platelet engraftment, acute GVHD, chronic GVHD, day 100 survival, and 1 year survival. A retrospective chart review was conducted on 61 pediatric patients who underwent BMT for malignant and non-malignant diseases from 7/1/2007 to 12/31/2014. To determine the effects of graft composition on engraftment and survival, Cox proportional hazards regression models were used with hazard ratios and 95% confidence intervals computed for each univariate model. Logistic regression models were used to determine the relationship of graft composition to acute and chronic GVHD with odds ratios and 95% confidence intervals computed for each univariate model. 28 patients (46%) underwent a related donor transplant, and 33 patients (54%) underwent an unrelated donor transplant. Grafts contained a median of 3.63 x 108 TNC/kg (range 0.031- 10.31 x 108/ kg), 4.09 x 106 CD34+/kg (range 0.76- 24.15 x 106/kg), and CD3+ 3.43 x 106/kg (range 0.0017-110.7 x 106/kg). Median time to engraftment was 17 days for neutrophils and 29 days for platelets. Interestingly, there was a trend for a relationship between increasing TNC and increasing time to neutrophil engraftment such that for every 1 x 108/kg unit increase in TNC there was a 12.5% decrease in the rate of neutrophil engraftment, HR 0.875 (0.765,1.001). A relationship was not seen between TNC and platelet engraftment, HR 0.979 (0.842, 1.137). Increasing CD34+ counts did shorten the time to platelet engraftment such that for every 1 x 10 6/kg unit increase in CD34+, there was an 8.5% increase in the risk of platelet engraftment, HR 1.085 (1.015, 1.161). A relationship was not identified between CD34+ and neutrophil engraftment, HR 1.040 (0.961, 1.124). CD3+ counts were not associated with neutrophil or platelet engraftment, HR 0.992 (0.976, 1.009) and 1.007 (0.990, 1.024) respectively. 18 (30%) of patients had grade 2 or higher aGVHD, and 8 (13%) of patients had cGVHD with no significant relationship seen with TNC, CD34+, or CD3+. Graft composition also did not have an effect on day 100 or 1 year survival, with the exception of a relationship between CD3+ and day 100
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Abstracts / Biol Blood Marrow Transplant 22 (2016) S19eS481
survival such that for every 1 x10 6/kg unit increase there was a 1.8% increased risk of death, HR 1.018 (1.001-1.036). Additional information is needed to help guide practice and has implications for choosing the target cell dose prior to a bone marrow harvest and the management of bone marrow donors.
follow up is 39 months (range 2-148). The 5-year probability of overall and leukemia-free survival for those receiving PB compared to BM was (61% versus 52%, p¼0.416) and (66% versus 43% p¼0.022) respectively. Conclusion: The use of PB compared to BM as a stem cell source from pediatric donors for children with acute leukemia is feasible and resulted in faster platelets recovery, significantly less relapse and improved leukemia-free survival.
351 Comparison of Peripheral Blood Versus Bone Marrow As Stem Cell Source from Matched-Related Donors on the Outcome of Allogeneic Hematopoietic Stem Cell Transplantation for Children with Acute Leukemia Ayad Ahmed Hussein 1, Rula Najjar2, Khadra Salami 3, Anas Haroun Haroun3, Rand Farraj3, Abdulhadi I. Al-Zaben 4, Haydar A. Frangoul 5. 1 Bone Marrow and Stem Cell Transplantation Program, King Hussein Cancer Center, Amman, Jordan; 2 king hussein cancer center, amman, Jordan; 3 King Hussein Cancer Center (KHCC), Amman, Jordan; 4 Bone Marrow and Stem Cell Transplantation Program, King Hussein Cancer Center, amman, Jordan; 5 The Children’s Hospital at TriStar Centennial and Sarah Cannon Reseach Institute, Nashville, TN Introduction: The effect of stem cell source on the outcome of children with acute leukemia following hematopoietic stem cell transplantation (HSCT) from fully matched related donor in countries with high rate of consanguinity and high incidence of CMV exposure, is not well known. Patients and Methods: We retrospectively reviewed the medical records of all children with acute leukemia who received matched-related HSCT at the Bone Marrow and Stem Cell Transplantation program at King Hussein Cancer Center (KHCC) in Amman, Jordan from January 2003 to December 2014. Results: A total of 111 patients were included, with a median age of 10 years (1-20) and 65 (58.5%) were males. Fifty-seven patients had ALL (51%) and 54 had AML (49%). Patients with ALL and those with AML beyond CR1 received TBI (1200 cGy)/Cy (120 mg/kg) conditioning. Patients with AML in CR1 received Bu (16 mg/kg)/Cy (200 mg/kg) conditioning. Ninety-three patients (83%) received peripheral blood (PB) and 18 patients (16.2%) received bone marrow (BM) as stem cell source. Patients who received PB and BM had similar age (p¼.714), sex (p¼0.115), CR status (p¼0.079), donor age (¼0.216), patient-donor sex-match (p¼0.215), and patientdonor CMV status matching (p¼0.999). There were more patients with ALL (p¼0.003) in the PBSC group. The median age of donors was 11 years (1-20) for PB group and 5 years (2 -23) for the BM group (p¼0.216). The median time to neutrophil engraftment for the PB and BM groups was 14 (10-23) and 13 days (11-22) , respectively (p¼ 0.861). The median time to platelet engraftment for the PB and BM groups was 14 (10-29) and 17 days (10-40), respectively (p¼ 0.006). The median hospitalization after stem cell infusion was 20 days (13-133) for the PB group and 19 days (17-35) for the BM group (p¼0.187). The incidence of CMV reactivation in the first 100 days following HSCT was 44% for PB group and 33% for the BM group (p¼0.398), and no CMV disease reported in both groups. The incidence of acute grade II-III GVHD was 35% for the PB group and 33% for the BM group (p¼0.9). There was a trend for higher incidence of chronic GVHD among the PB group compared to the BM group (35% versus 11% respectively p¼0.052). The transplant-related mortality (TRM) was 3% for patients who received PB and 0% for those who received BM (p¼0.999). There was significantly higher relapse rate among those who received BM compared to PB (55% versus 30% respectively p¼0.0372). The median
352 Allogeneic Hematopoietic Stem Cell Transplantation Using a Reduced Intensity Conditioning Regimen for Adolescents and Young Adults with Class 3 Beta-Thalassemia Ayad Ahmed Hussein 1, Abdulhadi I. Al-Zaben 2, Eman Khattab 3, Anas Haroun 1, Haydar A. Frangoul 4. 1 Bone Marrow and Stem Cell Transplantation Program, King Hussein Cancer Center, Amman, Jordan; 2 Bone Marrow and Stem Cell Transplantation Program, King Hussein Cancer Center, amman, Jordan; 3 King Hussein Cancer Center, Amman, Jordan; 4 The Children’s Hospital at TriStar Centennial and Sarah Cannon Reseach Institute, Nashville, TN Introduction: Although allogeneic hematopoietic stem cell transplantat (HSCT) can offer a curative approach for patients with thalassemia major, the reported outcome for adolescents and young adults (AYA) is inferior to that in children. Patients and Methods: We report on all consecutive patients 14 year of age with thalassemia major who received allogeneic HSCT from matched family donors at the Bone Marrow and Stem Cell Transplantation program at King Hussein Cancer Center (KHCC) in Amman, Jordan from January, 2004 until February, 2015. Results: Twenty-nine patients were included, with a median age of 17 year (range 14-28). The median ferritin level was 2980 ng/dl (270-10850). All patients had liver biopsy that showed evidence of liver fibrosis and were classified as Pesaro Class 3. Eleven patients (37%) had hepatitis B or C infection. Twelve patients (41%) underwent splenectomy prior to HSCT. All patients received reduced intensity conditioning (RIC) consisted of oral busulfan 2 mg/kg given every 12 hours on days -8 to -7, fludarabine 35 mg/m2 on days -6 to -2, ATG (horse 30 mg/kg for on days -6 to -2, or Rabitt 2.5 mg/kg on days -3 to -1) and total lymphoid irradiation (TLI) administered as a single fraction of 500 cGy on day zero prior to stem cell infusion. Cyclosporine and mycophenolate were used for GVHD prophylaxis. Peripheral blood stem cells from fully matched related donors was used in all patients. All patients achieved neutrophil and platelet engraftment at a median time of 14 (10-24) and 16 days (11-28), respectively. Three patients (10%) developed grade II skin acute GVHD. Chronic GVHD developed in 5 patients (17%), all were controlled with first line treatment. Secondary graft failure was observed in 3 (10%) patients, all of them are transfusion independent following a second RIC HSCT using the same preparative regimen without TLI. There was no transplant related mortality. At a median follow up of 28 months (6-130), all patients are alive and transfusion independent. The 3-year probability of overall and thalassemia-free survival was 100% and 90%, respectively. Conclusion: Using a TLI based RIC in AYA patients with high risk thalassemia major is very well tolerated and can result in an excellent thalassemia free survival.
empiric coverage in 60% of ST-related fevers, while in other 40% of cases, a different antibiotic(s) was used. The median length of antibiotic therapy was 72 hours (range 24-120) in 39 (66%) patients whose antibiotics were discontinued upon resolution of ST-related symptoms. In 20 (34%) patients, antibiotics were continued until resolution of neutropenia. Table 1 summarizes documented episodes of BSI during HCT using CDC/NHSN criteria. There were no episodes of gramnegative BSI during ST. Among 4 BSI during ST, only 1 (Coagulase negative staphylococci) occurred in a patient with ANC >500 at the start of ST. In patients with ANC>500 at the start of ST and a new fever, the risk of BSI is low (1/45; 2.2%; 95% CI 0.05-12%). Although fever resolved within 48 hours in 80% of patients, 82% of patients received >48 hours of empiric antibiotic therapy, due to the wait for negative culture results and extension of therapy in patients who became neutropenic during serotherapy. Prospective studies should address whether observation without antibiotics or use of shorter antibiotic courses is safe in children with ST-related fever and ANC>500.
349 Relationship of ABO Incompatible HSCT to Outcomes in Pediatric Patients Laura Jenkins 1, Elizabeth Garrett-Mayer 2, Elizabeth J. Williams 3, Elsie Hill 1, Cindy Kramer 3, Stacey Warneke 3, Jennifer Joi Jaroscak 4, Michelle Hudspeth 4. 1 Medical University of South Carolina, Charleston, SC; 2 Biostatistics, Medical University of South Carolina, Charleston, SC; 3 Blood and Marrow Transplant Program, Medical University of South Carolina, Charleston, SC; 4 Pediatric Hematology/Oncology, Medical University of South Carolina, Charleston, SC Minimal data exist regarding the impact of ABO incompatible transplants on outcomes of pediatric HSCT. We sought to determine the influence of ABO incompatibility on several outcomes in pediatric HSCT. We conducted a retrospective chart review of pediatric patients undergoing HSCT at our institution from 7/1/2007 to 7/1/2014 with at least 1 year of follow-up post-transplant. Four patients were excluded from the study, including two recipients of double cord blood transplants and two recipients of Rh incompatible transplants. Fisher’s exact test was used to compare baseline characteristics of the two groups. Median number of RBC and platelet transfusions were compared using the Wilcoxon rank sum test. Kaplan-Meier estimates were used to generate time to neutrophil engraftment and survival curves that were compared by the log-rank test. 38 patients received ABO compatible transplants, and 47 patients received ABO incompatible transplants within our time period. There was no statistically significant difference between the ABO compatible group and the ABO incompatible group with regards to diagnosis, preparative regimen, graft source, or degree of HLA match. 18 of the 47 patients (38%) who underwent ABO incompatible transplants switched to donor blood type within our follow-up period. Median time to neutrophil engraftment was 17 days for both groups. The median number of RBC and platelet transfusions required in the first 100 days following transplant did not significantly differ between the ABO compatible group (5.5 and 16) and the ABO incompatible group (8 and 13), p-values 0.54 and 0.59, respectively. The median survival, 2 year survival, and 5 year survival were not statistically significant between the ABO compatible
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group (3.21 yrs, 51%, and 46%) and the ABO incompatible group (5.64 yrs, 57%, and 54% ) with a p-value of 0.74. ABO incompatibility does not appear to affect neutrophil engraftment, early transfusion needs, or survival in pediatric HSCT. Findings should be validated in larger multiinstitution pediatric studies.
350 The Effect of Bone Marrow Graft Composition on Pediatric Bone Marrow Transplantation Outcomes Vanessa Fabrizio 1, Amy Wahlquist 2, Elsie Hill 1, Elizabeth J. Williams 3, Cindy Kramer 3, Jennifer Joi Jaroscak 4, Elizabeth Garrett-Mayer 2, Michelle Hudspeth 4. 1 Medical University of South Carolina, Charleston, SC; 2 Biostatistics, Medical University of South Carolina, Charleston, SC; 3 Blood and Marrow Transplant Program, Medical University of South Carolina, Charleston, SC; 4 Pediatric Hematology/Oncology, Medical University of South Carolina, Charleston, SC The cellular composition of the hematopoietic stem cell graft has generally been accepted to have an impact on transplantation outcomes. Recent studies have questioned this hypothesis for bone marrow grafts. A NMDP and CIBMTR study published in 2010 demonstrated a lack of effect of the composition of unrelated bone marrow donor grafts on outcomes but only included 44 pediatric recipients. We sought to determine if the infused TNC, CD34+ cell count, and CD3+ cell count had effects on neutrophil engraftment, platelet engraftment, acute GVHD, chronic GVHD, day 100 survival, and 1 year survival. A retrospective chart review was conducted on 61 pediatric patients who underwent BMT for malignant and non-malignant diseases from 7/1/2007 to 12/31/2014. To determine the effects of graft composition on engraftment and survival, Cox proportional hazards regression models were used with hazard ratios and 95% confidence intervals computed for each univariate model. Logistic regression models were used to determine the relationship of graft composition to acute and chronic GVHD with odds ratios and 95% confidence intervals computed for each univariate model. 28 patients (46%) underwent a related donor transplant, and 33 patients (54%) underwent an unrelated donor transplant. Grafts contained a median of 3.63 x 108 TNC/kg (range 0.031- 10.31 x 108/ kg), 4.09 x 106 CD34+/kg (range 0.76- 24.15 x 106/kg), and CD3+ 3.43 x 106/kg (range 0.0017-110.7 x 106/kg). Median time to engraftment was 17 days for neutrophils and 29 days for platelets. Interestingly, there was a trend for a relationship between increasing TNC and increasing time to neutrophil engraftment such that for every 1 x 108/kg unit increase in TNC there was a 12.5% decrease in the rate of neutrophil engraftment, HR 0.875 (0.765,1.001). A relationship was not seen between TNC and platelet engraftment, HR 0.979 (0.842, 1.137). Increasing CD34+ counts did shorten the time to platelet engraftment such that for every 1 x 10 6/kg unit increase in CD34+, there was an 8.5% increase in the risk of platelet engraftment, HR 1.085 (1.015, 1.161). A relationship was not identified between CD34+ and neutrophil engraftment, HR 1.040 (0.961, 1.124). CD3+ counts were not associated with neutrophil or platelet engraftment, HR 0.992 (0.976, 1.009) and 1.007 (0.990, 1.024) respectively. 18 (30%) of patients had grade 2 or higher aGVHD, and 8 (13%) of patients had cGVHD with no significant relationship seen with TNC, CD34+, or CD3+. Graft composition also did not have an effect on day 100 or 1 year survival, with the exception of a relationship between CD3+ and day 100
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Abstracts / Biol Blood Marrow Transplant 22 (2016) S19eS481
survival such that for every 1 x10 6/kg unit increase there was a 1.8% increased risk of death, HR 1.018 (1.001-1.036). Additional information is needed to help guide practice and has implications for choosing the target cell dose prior to a bone marrow harvest and the management of bone marrow donors.
follow up is 39 months (range 2-148). The 5-year probability of overall and leukemia-free survival for those receiving PB compared to BM was (61% versus 52%, p¼0.416) and (66% versus 43% p¼0.022) respectively. Conclusion: The use of PB compared to BM as a stem cell source from pediatric donors for children with acute leukemia is feasible and resulted in faster platelets recovery, significantly less relapse and improved leukemia-free survival.
351 Comparison of Peripheral Blood Versus Bone Marrow As Stem Cell Source from Matched-Related Donors on the Outcome of Allogeneic Hematopoietic Stem Cell Transplantation for Children with Acute Leukemia Ayad Ahmed Hussein 1, Rula Najjar2, Khadra Salami 3, Anas Haroun Haroun3, Rand Farraj3, Abdulhadi I. Al-Zaben 4, Haydar A. Frangoul 5. 1 Bone Marrow and Stem Cell Transplantation Program, King Hussein Cancer Center, Amman, Jordan; 2 king hussein cancer center, amman, Jordan; 3 King Hussein Cancer Center (KHCC), Amman, Jordan; 4 Bone Marrow and Stem Cell Transplantation Program, King Hussein Cancer Center, amman, Jordan; 5 The Children’s Hospital at TriStar Centennial and Sarah Cannon Reseach Institute, Nashville, TN Introduction: The effect of stem cell source on the outcome of children with acute leukemia following hematopoietic stem cell transplantation (HSCT) from fully matched related donor in countries with high rate of consanguinity and high incidence of CMV exposure, is not well known. Patients and Methods: We retrospectively reviewed the medical records of all children with acute leukemia who received matched-related HSCT at the Bone Marrow and Stem Cell Transplantation program at King Hussein Cancer Center (KHCC) in Amman, Jordan from January 2003 to December 2014. Results: A total of 111 patients were included, with a median age of 10 years (1-20) and 65 (58.5%) were males. Fifty-seven patients had ALL (51%) and 54 had AML (49%). Patients with ALL and those with AML beyond CR1 received TBI (1200 cGy)/Cy (120 mg/kg) conditioning. Patients with AML in CR1 received Bu (16 mg/kg)/Cy (200 mg/kg) conditioning. Ninety-three patients (83%) received peripheral blood (PB) and 18 patients (16.2%) received bone marrow (BM) as stem cell source. Patients who received PB and BM had similar age (p¼.714), sex (p¼0.115), CR status (p¼0.079), donor age (¼0.216), patient-donor sex-match (p¼0.215), and patientdonor CMV status matching (p¼0.999). There were more patients with ALL (p¼0.003) in the PBSC group. The median age of donors was 11 years (1-20) for PB group and 5 years (2 -23) for the BM group (p¼0.216). The median time to neutrophil engraftment for the PB and BM groups was 14 (10-23) and 13 days (11-22) , respectively (p¼ 0.861). The median time to platelet engraftment for the PB and BM groups was 14 (10-29) and 17 days (10-40), respectively (p¼ 0.006). The median hospitalization after stem cell infusion was 20 days (13-133) for the PB group and 19 days (17-35) for the BM group (p¼0.187). The incidence of CMV reactivation in the first 100 days following HSCT was 44% for PB group and 33% for the BM group (p¼0.398), and no CMV disease reported in both groups. The incidence of acute grade II-III GVHD was 35% for the PB group and 33% for the BM group (p¼0.9). There was a trend for higher incidence of chronic GVHD among the PB group compared to the BM group (35% versus 11% respectively p¼0.052). The transplant-related mortality (TRM) was 3% for patients who received PB and 0% for those who received BM (p¼0.999). There was significantly higher relapse rate among those who received BM compared to PB (55% versus 30% respectively p¼0.0372). The median
352 Allogeneic Hematopoietic Stem Cell Transplantation Using a Reduced Intensity Conditioning Regimen for Adolescents and Young Adults with Class 3 Beta-Thalassemia Ayad Ahmed Hussein 1, Abdulhadi I. Al-Zaben 2, Eman Khattab 3, Anas Haroun 1, Haydar A. Frangoul 4. 1 Bone Marrow and Stem Cell Transplantation Program, King Hussein Cancer Center, Amman, Jordan; 2 Bone Marrow and Stem Cell Transplantation Program, King Hussein Cancer Center, amman, Jordan; 3 King Hussein Cancer Center, Amman, Jordan; 4 The Children’s Hospital at TriStar Centennial and Sarah Cannon Reseach Institute, Nashville, TN Introduction: Although allogeneic hematopoietic stem cell transplantat (HSCT) can offer a curative approach for patients with thalassemia major, the reported outcome for adolescents and young adults (AYA) is inferior to that in children. Patients and Methods: We report on all consecutive patients 14 year of age with thalassemia major who received allogeneic HSCT from matched family donors at the Bone Marrow and Stem Cell Transplantation program at King Hussein Cancer Center (KHCC) in Amman, Jordan from January, 2004 until February, 2015. Results: Twenty-nine patients were included, with a median age of 17 year (range 14-28). The median ferritin level was 2980 ng/dl (270-10850). All patients had liver biopsy that showed evidence of liver fibrosis and were classified as Pesaro Class 3. Eleven patients (37%) had hepatitis B or C infection. Twelve patients (41%) underwent splenectomy prior to HSCT. All patients received reduced intensity conditioning (RIC) consisted of oral busulfan 2 mg/kg given every 12 hours on days -8 to -7, fludarabine 35 mg/m2 on days -6 to -2, ATG (horse 30 mg/kg for on days -6 to -2, or Rabitt 2.5 mg/kg on days -3 to -1) and total lymphoid irradiation (TLI) administered as a single fraction of 500 cGy on day zero prior to stem cell infusion. Cyclosporine and mycophenolate were used for GVHD prophylaxis. Peripheral blood stem cells from fully matched related donors was used in all patients. All patients achieved neutrophil and platelet engraftment at a median time of 14 (10-24) and 16 days (11-28), respectively. Three patients (10%) developed grade II skin acute GVHD. Chronic GVHD developed in 5 patients (17%), all were controlled with first line treatment. Secondary graft failure was observed in 3 (10%) patients, all of them are transfusion independent following a second RIC HSCT using the same preparative regimen without TLI. There was no transplant related mortality. At a median follow up of 28 months (6-130), all patients are alive and transfusion independent. The 3-year probability of overall and thalassemia-free survival was 100% and 90%, respectively. Conclusion: Using a TLI based RIC in AYA patients with high risk thalassemia major is very well tolerated and can result in an excellent thalassemia free survival.