ABSTRACT
The Children's Cancer Group (CCG) 1952 clinical trial for children with standard-risk acute lymphoblastic leukemia (SR-ALL) compared intrathecal (IT) methotrexate (MTX) with IT triples (ITT) (MTX, cytarabine, and hydrocortisone sodium succinate [HSS]) as presymptomatic central nervous system (CNS) treatment. Following remission induction, 1018 patients were randomized to receive IT MTX and 1009 ITT. Multivariate analysis identified male sex, hepatomegaly, CNS-2 status, and age younger than 2 or older than 6 years as significant predictors of isolated CNS (iCNS) relapse. The 6-year cumulative incidence estimates of iCNS relapse are 3.4% +/- 1.0% for ITT and 5.9% +/- 1.2% for IT MTX; P = .004. Significantly more relapses occurred in bone marrow (BM) and testicles with ITT than IT MTX, particularly among patients with T-cell phenotype or day 14 BM aspirate containing 5% to 25% blasts. Thus, the estimated 6-year event-free survivals (EFS) with ITT or IT MTX are equivalent at 80.7% +/- 1.9% and 82.5% +/- 1.8%, respectively (P = .3). Because the salvage rate after BM relapse is inferior to that after CNS relapse, the 6-year overall survival (OS) for ITT is 90.3% +/- 1.5% versus 94.4% +/- 1.1% for IT MTX (P = .01). It appears that ITT improves presymptomatic CNS treatment but does not improve overall outcome.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Central Nervous System Neoplasms/drug therapy , Central Nervous System Neoplasms/secondary , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Age Factors , Antimetabolites, Antineoplastic/administration & dosage , Bone Marrow Neoplasms/secondary , Central Nervous System/pathology , Central Nervous System Neoplasms/mortality , Child , Child, Preschool , Cytarabine/administration & dosage , Disease-Free Survival , Female , Humans , Hydrocortisone/administration & dosage , Hydrocortisone/analogs & derivatives , Injections, Spinal , Male , Methotrexate/administration & dosage , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Recurrence , Remission Induction , Retrospective Studies , Risk Factors , Sex Factors , T-Lymphocytes/pathology , Testicular Neoplasms/secondary , Time FactorsABSTRACT
Acute leukemia is an untoward event following immunosuppression for solid organ transplantation and is related to the oncogenic effects of Epstein-Barr viral infections. The authors report a case of acute, Philadelphia chromosome-positive, T-cell lymphoblastic leukemia following liver transplantation. Molecular typing demonstrated a minor bcr-abl rearrangement (190 kD), which persisted in remission in 71% of peripheral neutrophils as determined by fluorescence in situ hybridization. The authors conclude that this patient may have presented in a lymphoid blast crisis of chronic myelogenous leukemia with an acute T-cell leukemia/lymphoma syndrome.