Subject(s)
Autoimmune Diseases/drug therapy , Hemophilia A/drug therapy , Lenalidomide/therapeutic use , Autoantibodies/immunology , Autoimmune Diseases/complications , Autoimmune Diseases/pathology , Drug Eruptions/etiology , Drug Substitution , Factor VIII/immunology , Hemophilia A/complications , Hemophilia A/pathology , Hemorrhage/complications , Humans , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Lenalidomide/adverse effects , Male , Middle Aged , Paraplegia/etiology , Spinal Cord/blood supplyABSTRACT
With the increasing age of patients undergoing allogeneic hematopoietic cell transplantation (HCT), the age of matched related sibling donors (MRDs) is expected to increase. Donor safety and the impact of donors' age on mobilization, collection of peripheral hematopoietic progenitor cells (HPCs), subsequent engraftment and the incidence of GVHD were retrospectively analyzed. A total of 167 patients received HCT from an MRD. Median donors' age was 48 years (67 (40%) donors were ≥50 years including 34 donors ≥60 years). Side effects under mobilization and apheresis were age independent. Grafts from donors <50 years contained more CD34+ cells (median 9 × 10(6)/kg recipient's body weight (RBW)) compared with older donors (median 5.9 × 10(6)/kg RBW) (P<0.0005), whereas harvests from donors ≥60 years contained more natural killer (NK) cells (P=0.003). Engraftment occurred at a median of 12 days after HCT irrespective of donors' age. Increasing age of MRD did not preclude successful mobilization, collection of HPC and engraftment. In the context of more NK cells in grafts from elderly donors, the impact of donors' age on outcome after HCT warrants further studies. Although short-term toxicities of apheresis were not increased with increasing age, long-term donor safety remains an important issue.
Subject(s)
Hematopoietic Stem Cell Mobilization/methods , Hematopoietic Stem Cell Transplantation/methods , Hematopoietic Stem Cells/immunology , Adolescent , Adult , Aged , Chimerism , Female , Humans , Male , Middle Aged , Retrospective Studies , Siblings , Transplantation, Homologous , Young AdultABSTRACT
Kinetics of BCR-ABL transcript elimination and its prognostic implications on relapse were analyzed in patients with chronic myeloid leukemia (CML) after reduced intensity hematopoietic cell transplantation (HCT). In all, 19 CML patients were conditioned with 2 Gy total-body irradiation in combination with (n=14) or without (n=3) fludarabine 3 x 30 mg/m(2) (Flu) or 4.5 Gy total lymphoid irradiation (TLI) with Flu and OKT3 3 x 5 mg (n=2) and were treated with cyclosporine (CSP) and mycophenolate mofetil after allogeneic HCT. BCR-ABL transcripts were analyzed by nested RT-PCR and Taqman((R)) RT-PCR on days +28, +56 and +84 after HCT and were evaluated for their association with relapse. Of the 19 patients, 14 achieved sustained remissions of which six had a negative RT-PCR 28 days after HCT. Five patients relapsed +41, +54, +57, +136 and +234 days after HCT. Predictors for relapse were advanced disease stage (P=0.02) and slow reduction of BCR-ABL transcripts at day 28 (P=0.006) and day 56 (P=0.047) post-transplant. We conclude that a complete clearance of BCR-ABL transcripts is achievable within 4 weeks from HCT even after minimal conditioning and that early kinetics of BCR-ABL transcripts significantly correlate with the probability of hematological relapse.
