Subject(s)
Anemia, Aplastic/therapy , Antilymphocyte Serum/administration & dosage , Cord Blood Stem Cell Transplantation , Transplantation Conditioning , Unrelated Donors , Allografts , Anemia, Aplastic/mortality , Antilymphocyte Serum/adverse effects , Child , Child, Preschool , Follow-Up Studies , Humans , Infant , Male , Retrospective StudiesABSTRACT
Recent studies revealed that a substantial proportion of patients with high-risk B-cell precursor acute lymphoblastic leukemia (BCP-ALL) harbor fusions involving tyrosine kinase and cytokine receptors, such as ABL1, PDGFRB, JAK2 and CRLF2, which are targeted by tyrosine kinase inhibitors (TKIs). In the present study, transcriptome analysis or multiplex reverse transcriptase-PCR analysis of 373 BCP-ALL patients without recurrent genetic abnormalities identified 29 patients with kinase fusions. Clinically, male predominance (male/female: 22/7), older age at onset (mean age at onset: 8.8 years) and a high white blood cell count at diagnosis (mean: 94 200/µl) reflected the predominance of National Cancer Institute high-risk (NCI-HR) patients (NCI-standard risk/HR: 8/21). Genetic analysis identified three patients with ABL1 rearrangements, eight with PDGFRB rearrangements, two with JAK2 rearrangements, three with IgH-EPOR and one with NCOR1-LYN. Of the 14 patients with CRLF2 rearrangements, two harbored IgH-EPOR and PDGFRB rearrangements. IKZF1 deletion was present in 16 of the 22 patients. The 5-year event-free and overall survival rates were 48.6±9.7% and 73.5±8.6%, respectively. The outcome was not satisfactory without sophisticated minimal residual disease-based stratification. Furthermore, the efficacy of TKIs combined with conventional chemotherapy without allogeneic hematopoietic stem cell transplantation in this cohort should be determined.
Subject(s)
Oncogene Proteins, Fusion/genetics , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Protein Interaction Domains and Motifs/genetics , Protein-Tyrosine Kinases/genetics , Adolescent , Biomarkers, Tumor , Child , Child, Preschool , Cohort Studies , Combined Modality Therapy , Female , Gene Deletion , Genetic Predisposition to Disease , Humans , Ikaros Transcription Factor/genetics , Infant , Janus Kinase 2/genetics , Japan , Male , Mutation , Oncogene Proteins, Fusion/chemistry , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/mortality , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/therapy , Prognosis , Proportional Hazards Models , Treatment OutcomeSubject(s)
Hematologic Neoplasms/epidemiology , Hematologic Neoplasms/etiology , Hematopoietic Stem Cell Transplantation/methods , Adolescent , Adult , Child , Cord Blood Stem Cell Transplantation/adverse effects , Female , Humans , Incidence , Japan , Kaplan-Meier Estimate , Male , Middle Aged , Risk Factors , Tissue Donors , Transplantation, Homologous , Young AdultABSTRACT
The outcome of 55 children with severe aplastic anemia (SAA) who received a second hematopoietic stem cell transplantation (HSCT) was retrospectively analyzed using the registration data of the Japanese Society for Hematopoietic Cell Transplantation. The 5-year overall survival (OS) and failure-free survival (FFS) after the second transplantation were 82.9% (95% confidence interval (CI), 69.7-90.8)) and 81.2% (95% CI, 67.8-89.4), respectively. FFS was significantly better when the interval between the first and second transplantation was >60 days (88.9%; 95% CI, 73.0-95.7) than when it was ⩽60 days (61.4%; 95% CI, 33.3-80.5; P=0.026). All 12 patients who were conditioned with regimens containing fludarabine and melphalan were alive with hematopoietic recovery. These findings justify the recommendation of a second HSCT for children with SAA who have experienced graft failure after first HSCT.
Subject(s)
Anemia, Aplastic/therapy , Hematopoietic Stem Cell Transplantation/methods , Transplantation Conditioning/methods , Transplantation, Homologous/methods , Adolescent , Anemia, Aplastic/mortality , Child , Child, Preschool , Female , Humans , Infant , Male , Survival AnalysisABSTRACT
Primary graft failure (pGF) is associated with considerable morbidity and mortality. Salvage hematopoietic SCT (HSCT) can rescue pGF patients; however, the optimal preconditioning regimen and stem cell source are yet to be determined, particularly in children. In this study, we retrospectively analyzed 102 pediatric patients who received salvage allogeneic HSCT for pGF. Salvage HSCT from matched or one-Ag-mismatched related donors (rMM01) provided superior OS compared with that from two- or three-Ags-mismatched related donors (rMM23) or cord blood transplantation (CBT). CBT showed a trend toward a slightly lower engraftment rate and late engraftment achievement compared with rMM23; however, the OS rate was similar between the two groups (47.6±7.7% for rMM23 and 45.7±8.6% for CBT, at 1 year after salvage HSCT). Multivariate analysis showed that preconditioning regimens with fludarabine or irradiation were associated with a higher engraftment rate and those with alkylating agents were associated with better OS. In conclusion, our results showed that rMM01 was the most suitable donor for salvage HSCT for pediatric pGF, and that CBT was an equally important option compared with rMM23 for patients without rMM01.
Subject(s)
Graft Rejection/surgery , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/methods , Salvage Therapy/methods , Transplantation Conditioning/methods , Adolescent , Child , Child, Preschool , Graft Survival , Humans , Infant , Prognosis , Risk Factors , Survival Rate , Transplantation, Homologous , Treatment OutcomeSubject(s)
Cancer Vaccines/therapeutic use , Hematopoietic Stem Cell Transplantation , Leukemia/therapy , WT1 Proteins/chemistry , WT1 Proteins/therapeutic use , Adolescent , Child , Child, Preschool , Combined Modality Therapy , Female , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Infant , Leukemia/genetics , Leukemia/immunology , Male , Peptides/chemistry , Peptides/immunology , RNA, Messenger/analysis , RNA, Messenger/genetics , Recurrence , Risk , T-Lymphocytes, Cytotoxic/immunology , Transplantation, Homologous , WT1 Proteins/genetics , WT1 Proteins/immunologyABSTRACT
In all, 100 unrelated donor bone marrow transplantations (UD-BMT) were performed in our institute between October 1993 and January 2003. Of 93 evaluable patients, 73 patients had hematological malignancy, 13 had nonmalignancy and seven had lymphoproliferative disease. The estimated 9-year event-free survival (EFS) rate was 57.1+/-5.5% in all patients. In the following analyses of the patients with hematological malignancy, the standard group had significantly better EFS than the high-risk group (61.5+/-7.0 vs 35.6+/-9.7%, P=0.02), and the EFS rate of the tacrolimus (FK-506)+methotrexate (MTX)+/-methylprednisolone prophylactic group for graft-versus-host disease was superior to that of the FK-506 without MTX group (75.7+/-8.0 vs 55.8+/-7.6%, P=0.02). When we compared the EFS rates of the FK506+MTX+/-methylprednisolone (mPSL) group and the HLA-matched related donor BMT group in our institute, these were almost similar (75.7+/-8.1 vs 68.4+/-9.3%). Therefore, UD-BMT using FK-506+MTX+/-mPSL is a safe and useful method for children with hematological malignancy who require allogeneic BMT.
