ABSTRACT
The prognosis of relapsed/refractory (R/R) pediatric acute leukemia is extremely poor. We retrospectively reviewed 20 consecutive pediatric patients with R/R acute leukemia who underwent a first HLA-haploidentical peripheral blood stem cell transplantation following reduced-intensity conditioning (haplo-RIC-PBSCT) with very low-dose antithymocyte globulin (ATG) between 2012 and 2019. Of these 20 patients, 7 patients had acute lymphoblastic leukemia, and 13 had acute myeloid leukemia. At the time of haplo-RIC-PBSCT, 15 patients had active disease. The median follow-up duration for survivors was 56 months (range 22-108 months). Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus, short-term methotrexate, methylprednisolone, and ATG 1.25 mg/kg on day-2. The 2-year cumulative incidence of transplant-related mortality and relapse were 5.0% [95% confidence interval (CI) 0.7-30.5%)] and 57.8% (95% CI 37.4-79.6%), respectively. Among the 20 patients, 16 (80.0%) developed grade III-IV acute GVHD, and 2 developed severe chronic GVHD. The 2-year event-free survival and overall survival rates were 40.0% (95% CI 19.3-60.0%) and 50.0% (95% CI 27.1-69.2%), respectively. Although the sample size is small, the survival outcomes of the present study are encouraging.
Subject(s)
Antilymphocyte Serum/administration & dosage , HLA Antigens/genetics , Haploidy , Leukemia, Myeloid, Acute/surgery , Peripheral Blood Stem Cell Transplantation/methods , Precursor Cell Lymphoblastic Leukemia-Lymphoma/surgery , Transplantation Conditioning/methods , Adolescent , Age Factors , Child , Child, Preschool , Female , Follow-Up Studies , Graft vs Host Disease/epidemiology , Graft vs Host Disease/etiology , Graft vs Host Disease/prevention & control , Humans , Infant , Leukemia, Myeloid, Acute/mortality , Male , Peripheral Blood Stem Cell Transplantation/adverse effects , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Recurrence , Retrospective Studies , Survival Rate , Treatment OutcomeABSTRACT
The rejection rate in cord blood transplants for chronic Epstein-Bar virus-associated T or natural killer cell lymphoproliferative diseases using our standard reduced-intensity conditioning "LPAM140 regimen," which includes fludarabine, melphalan (LPAM), etoposide, and antithymocyte globulin, has been high. To ensure better engraftment, we increased the LPAM dose to 210 mg/m2 ("LPAM210 regimen"). Patient data (n = 22; LPAM140, n = 7; LPAM210, n = 15) were analyzed retrospectively. The engraftment rate after the LPAM210 regimen (100.0%) was significantly higher than that after the LPAM140 regimen (57.1%; P = .002). Fludarabine combined with melphalan (210 mg/m2 ) had a favorable impact on engraftment.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cord Blood Stem Cell Transplantation/adverse effects , Epstein-Barr Virus Infections/complications , Graft vs Host Disease/etiology , Herpesvirus 4, Human/isolation & purification , Lymphoproliferative Disorders/therapy , Adolescent , Adult , Antilymphocyte Serum/administration & dosage , Child , Child, Preschool , Combined Modality Therapy , Epstein-Barr Virus Infections/virology , Etoposide/administration & dosage , Female , Follow-Up Studies , Graft vs Host Disease/metabolism , Graft vs Host Disease/pathology , Humans , Infant , Infant, Newborn , Killer Cells, Natural/immunology , Killer Cells, Natural/virology , Lymphoproliferative Disorders/immunology , Lymphoproliferative Disorders/pathology , Lymphoproliferative Disorders/virology , Male , Melphalan/administration & dosage , Prognosis , Retrospective Studies , Survival Rate , T-Lymphocytes/immunology , T-Lymphocytes/virology , Transplantation Conditioning , Transplantation, Homologous , Vidarabine/administration & dosage , Vidarabine/analogs & derivatives , Young AdultABSTRACT
Leukemic relapse in the central nervous system (CNS) after conventional treatment is associated with a poor prognosis. The effectiveness and safety of IV infusion of human leukocyte antigen (HLA)-mismatched lymphocytes for leukemia, and intrathecal (IT) infusion of HLA-mismatched lymphocytes for cerebrospinal fluid (CSF) dissemination of medulloblastoma have been reported. A 13-year-old girl (HLA-A31) was diagnosed as relapsing from Philadelphia chromosome-positive acute leukemia in the CNS after receiving chemotherapy, tyrosine kinase inhibitors, haploidentical hematopoietic stem cell transplantation (HSCT) from her father (HLA-A31), and craniospinal irradiation. We performed an IT infusion of haploidentical lymphocytes from her mother. Peripheral blood mononuclear cells obtained from her mother (HLA-A31) were administered by IT infusion weekly. Examination of CSF 1 week after first IT showed that lymphocyte counts had increased markedly and the breakpoint cluster region/abelson-bearing cells had disappeared. Furthermore, CD3 T cells in the CSF were negative for HLA-A31, and expressed high HLA-DR. These results indicate the infused non-HSCT-donor lymphocytes did not survive, and that the HSCT donor(father)-derived lymphocytes migrated to the CSF and were activated. The patient showed partial remission for 2 months following this therapy. Serious adverse reactions and graft versus host disease were not observed. To control leukemic CNS dissemination, haploidentical nondonor lymphocytes might contribute to a graft versus leukemia effect.
Subject(s)
Central Nervous System Neoplasms/therapy , Immunotherapy, Adoptive/methods , Leukemia, Myeloid, Acute/therapy , Leukocytes, Mononuclear/transplantation , Neoplasm Recurrence, Local/therapy , Adolescent , Female , Hematopoietic Stem Cell Transplantation , Humans , Injections, SpinalABSTRACT
Simpson-Golabi-Behmel syndrome is a congenital malformation syndrome associated with mutations in GPC3, which is located in the Xq26 region. Three new loss-of-function mutations and a global X-chromosome rearrangement involving GPC3 were identified. A female sibling of the patient, who presented with a cleft palate and hepatoblastoma, carries the same chromosomal rearrangement and a paradoxical pattern of X-chromosome inactivation. These findings support variable GPC3 alterations, with a possible mechanism in female patients.
ABSTRACT
A 16-month-old girl was diagnosed with Epstein-Barr virus hemophagocytic lymphohistiocytosis and transferred to our hospital on the 58th day of the hemophagocytic lymphohistiocytosis after treatment failure according to the Hemophagocytic Lymphohistiocytosis-2004 protocol. On admission to our hospital, she had a flaccid paralysis of her lower limbs. Nerve conduction studies showed a acute motor axonal neuropathy, and a diagnosis of Guillain-Barre syndrome was established. Intravenous immunoglobulin G was started on the 57th day of the Guillain-Barre syndrome. To date, her neurological recovery is incomplete. For hemophagocytic lymphohistiocytosis, after treatment failure of THP-COP regimen (pirarubicin, cyclophosphamide, vincristine, and prednisone) and 2 courses of ESCAP regimen (etoposide, prednisone, cytarabine, L-asparaginase), we are now in the process of coordinating unrelated umbilical cord blood transplantation. To the best of our knowledge, we report the youngest case of Guillain-Barre syndrome accompanied by Epstein-Barr virus hemophagocytic lymphohistiocytosis. Rapid progression of Guillain-Barre syndrome, the electrophysiological subtype of Guillain-Barre syndrome, and treatment delay possibly led to poor neurological outcome.
