Subject(s)
Hematopoietic Stem Cell Transplantation/methods , Respiratory Function Tests/methods , Transplantation Conditioning/methods , Adolescent , Adult , Busulfan/therapeutic use , Child , Child, Preschool , Female , Hematopoietic Stem Cell Transplantation/standards , Humans , Lung Diseases/etiology , Male , Myeloablative Agonists/therapeutic use , Transplantation Conditioning/adverse effects , Transplantation Conditioning/standards , Vidarabine/analogs & derivatives , Vidarabine/therapeutic use , Young AdultSubject(s)
Central Nervous System Neoplasms/prevention & control , Cytarabine/administration & dosage , Hematopoietic Stem Cell Transplantation/methods , Leukemia/pathology , Lymphoma, Non-Hodgkin/pathology , Neoplasm Invasiveness/prevention & control , Acute Disease , Adolescent , Adult , Antimetabolites, Antineoplastic/therapeutic use , Antimetabolites, Antineoplastic/toxicity , Child , Cytarabine/toxicity , Humans , Liposomes , Treatment Outcome , Young AdultABSTRACT
There is a significant amount of morbidity and mortality following myeloablative umbilical cord blood transplantation (UCBT). Reduced intensity (RI) conditioning offers an alternative to myeloablative conditioning before UCBT. We investigated RI-UCBT in 21 children and adolescents with malignant (n=14), and non-malignant diseases (n=7). RI conditioning consisted of fludarabine (150-180 mg/m2) with either busulfan (< or = 8 mg/kg)+rabbit antithymocyte globulin (R-ATG; n=16) or cyclophosphamide+R-ATG+/-etoposide (n=5). Human leukocyte antigen match: 4/6 (n=13), 5/6 (n=5) and 6/6 (n=3). The median total nucleated cell and CD34+ cell dose per kilogram were 3.58 x 10(7) and 2.54 x 10(5), respectively. The median time for neutrophil and platelet engraftment was 17.5 and 52 days, respectively. There were six primary graft failures (chronic myelogenous leukemia (CML), beta-thalassemia, hemophagocytic lymphohistiocytosis (HLH) and myelodysplastic syndrome (MDS)). The probability of developing grade II to grade IV acute graft-versus-host disease (GVHD) and chronic GVHD was 28.6 and 16.7%, respectively. Incidence of transplant-related mortality (TRM) was 14%. The 5 years overall survival (OS) in all patients was 59.8%. The 5 years OS for patients with average versus poor-risk malignancy was 77.8 versus 22.2% (P=0.03). RI-UCBT may result in graft failure in specific high-risk chemo-naïve patients (CML, beta-thalassemia, HLH and MDS), but in more heavily pretreated pediatric and adolescent recipients results in rapid engraftment and may be associated with decreased severe GVHD and TRM.
Subject(s)
Cord Blood Stem Cell Transplantation/methods , Fetal Blood/cytology , Neoplasms/therapy , Adolescent , Adult , Antigens, CD34/analysis , Child , Child, Preschool , Graft vs Host Disease/prevention & control , Granulocyte-Macrophage Colony-Stimulating Factor/therapeutic use , Humans , Immunologic Factors/therapeutic use , Living Donors , Myelodysplastic Syndromes/mortality , Myelodysplastic Syndromes/therapy , Neoplasms/mortality , Patient Selection , Recombinant Proteins , Survival Analysis , Transplantation Chimera , Transplantation Conditioning , Treatment Failure , Treatment Outcome , beta-Thalassemia/mortality , beta-Thalassemia/therapyABSTRACT
We report results of unrelated cord blood transplants (UCBT) in 29 pediatric recipients in one center and the risk factors associated with survival. Median age: 9 years (0.5-20); diagnosis: ALL (9), AML (4), CML (1), HD (3), HLH (1), NHL (3), NBL (2); B-thal (1), FA (1), FEL (1), Krabbe (1), WAS (1), SAA (1); median follow-up: 11 months; conditioning: total body irradiation (TBI)-ablative (14), chemotherapy-ablative (6) and reduced intensity chemotherapy (9); GVHD prophylaxis: MMF/FK506 (18), cyclosporin A (CsA)+steroids+/-MMF (7) or CsA+methotrexate (MTX) (4); median total nucleated cells (TNC): 3.8 x 10(7)/kg (1.1-11); median CD34+: 2.3 x 10(5)/kg (0.2-9.9); and HLA match: 2 (6/6), 5 (5/6), 22 (4/6). Neutrophil engraftment by cumulative incidence curves 63% (median 28 (95% confidence interval (CI) 18-32)). Probability of >/=grade II acute graft-versus-host disease (aGVHD) by day +60 27%, >/=grade III aGVHD 20% and chronic graft-versus-host disease 3%. Estimated 1-year overall survival (OS) 46% (95% CI 30-71) and standard risk 60% (95% CI 29-100%). Variables associated with improved survival by multivariate analysis include non-TBI-ablative conditioning (P=0.024), CD34+/kg (P=0.038) and gender (P=0.048). These results suggest that CD34/kg cell dose and non-TBI-ablative conditioning may be important variables influencing OS following UCBT in pediatric recipients. Given the small number of patients, these results should be viewed cautiously.
Subject(s)
Cord Blood Stem Cell Transplantation , Adolescent , Adult , Antigens, CD34/analysis , Blood Donors , Child , Child, Preschool , Cohort Studies , Cord Blood Stem Cell Transplantation/adverse effects , Cord Blood Stem Cell Transplantation/methods , Cord Blood Stem Cell Transplantation/mortality , Female , Graft vs Host Disease/etiology , Graft vs Host Disease/prevention & control , Hematologic Neoplasms/complications , Hematologic Neoplasms/mortality , Hematologic Neoplasms/therapy , Histocompatibility , Histocompatibility Testing , Humans , Infant , Male , Probability , Prognosis , Survival Analysis , Treatment OutcomeABSTRACT
Reduced intensity (RI) allogeneic stem cell transplantation (AlloSCT) was initially demonstrated in adults following HLA-matched family and unrelated adult donor AlloSCT. There is little information about RI AlloSCT in children. We report results of a pilot study of RI AlloSCT in 21 recipients (< or =21 years). Age: median 13 (0.5-21) years, 8F:13M, 14 unrelated cord blood units (UCB) (10 4/6, 4 5/6), two related BM (6/6, 5/6), four related PBSC (2 6/6, 2 5/6), and one related BM+PBSC (6/6). RI: fludarabine, busulfan (n=14); fludarabine, cyclophosphamide (n=4); fludarabine, melphalan (n=1); total body irradiation, fludarabine, cyclophosphamide (n=1); or fludarabine, cyclophosphamide, and etoposide (n=1). Graft-versus-host disease prophylaxis: FK506 0.03 mg/kg/day and mycophenolate mofetil 15 mg/kg/q 12 h. UCB median nuc/kg and CD34/kg was 4.3 x 10(7)/kg (0.9-10.8) and 1.9 x 10(5)/kg (0.3-6.9), and related BM/PBSC median nuc/kg and CD34/kg was 8.3 x 10(8) (4.7-18.9) and 5.0 x 10(6)/kg (4.6-6.4). Maximal chimerism following unrelated cord blood transplantation, 100% x 7, 98% x 1, 95% x 2, 55% x 1, and 0% x 3; related PBSC/BM, 100% x 5, 65% x 1, and 55% x 1. Graft failure occurred in 5/21 (24%). In summary, RI AlloSCT in children is feasible and tolerable (< or =25% GF) and results in > or =85% of recipients initially achieving > or =50% donor chimerism.
