Theodore F. Zipf

Measurement of Residual Leukemia during Remission in Childhood Acute Lymphoblastic Leukemia

BACKGROUND Complete remission of B-precursor acute lymphoblastic leukemia (ALL) has traditionally been defined as the near absence of lymphoblasts in a light-microscopical examination of stained bone marrow smears, but a patient in remission may still harbor up to 10(10) leukemia cells. We investigated whether there is a relation between the outcome of treatment and submicroscopic evidence of residual disease. METHODS We conducted a prospective study of patients during a first clinical remission using a quantitative polymerase-chain-reaction (PCR) assay capable of detecting 1 viable leukemia cell among 200,000 normal marrow mononuclear cells and a clonogenic blast-colony assay. Bone marrow specimens from 24 children were sequentially evaluated during a five-year period, and the results were compared with the clinical outcome. RESULTS Seven patients relapsed and 17 remained in remission 2 to 35 months after the completion of treatment. The levels of residual leukemia-cell DNA in the two groups were significantly different (P<0.001; 95 percent confidence interval for the difference in the mean log-transformed ratio of leukemia-cell DNA to normal bone marrow-cell DNA, 0.38 to 1.28). Autoregression analyses identified trends for individual patients that were associated with relapse. Despite continued remission in 17 patients, evidence of residual leukemia was detected by PCR in 15 and by both PCR and blast-colony assays in 7. CONCLUSIONS Molecular signs of residual leukemia can persist up to 35 months after the cessation of chemotherapy in children with ALL in remission. This suggests that eradication of all leukemia cells may not be a prerequisite for cure.

Outpatient treatment of fever and neutropenia for low risk pediatric cancer patients

Fever and neutropenia (F&N) is a common complication of cancer chemotherapy. It is conveniently managed by hospitalization and empiric administration of parenteral antibiotics. This study attempted to determine whether pediatric cancer patients with F&N identified as low risk for morbidity and mortality by clinical criteria at the time of presentation could be treated safely as outpatients.

Minocycline-Ethylenediaminetetraacetate Lock Solution for the Prevention of Implantable Port Infections in Children with Cancer

In this prospective cohort study, minocycline-ethylenediaminetetraacetate (M-EDTA) was used as a lock solution in indwelling ports inserted in 14 children with cancer. No port infections, thrombotic events, or other adverse events were observed, compared with 10 port infections that occurred in 48 control patients whose ports were flushed with heparin. M-EDTA is a promising lock solution in long-term catheters.

Economic and resource utilization analysis of outpatient management of fever and neutropenia in low-risk pediatric patients with cancer

PURPOSE To measure resource allocation in outpatient management of fever and neutropenia in low-risk pediatric patients with cancer and its impact on their families. PATIENTS AND METHODS A prospective clinical trial was conducted. Eligible patients received a single dose of intravenous (IV) antibiotics and were observed for several hours in clinic. Patients were randomly assigned to continue either IV or oral antibiotics and were seen daily as outpatients. Charges were calculated based on the number of resources used and Medicare/Medicaid reimbursement schedules. A questionnaire was used to measure the impact of outpatient treatment on the family. RESULTS Seventy-three episodes of fever and neutropenia were studied. The median duration of treatment was 4 days. Eighty-six percent of the episodes were managed without hospitalization. The median calculated charge was

The clinical significance of residual disease in childhood acute lymphoblastic leukemia as detected by polymerase chain reaction amplification of antigen-receptor gene sequences

1840. The median calculated charge for patients receiving oral antibiotics was

Molecular monitoring of cerebrospinal fluid can predict clinical relapse in acute lymphoblastic leukemia with eosinophilia.

1544 and was significantly less than the

Residual leukaemia after bone marrow transplant in children with acute lymphoblastic leukaemia after first haematological relapse or with poor initial presenting features

2039 median charge for outpatients treated with IV antibiotics. The estimated charge for comparable inpatient treatment was

VESICULAR GRAFT‐VERSUS‐HOST DISEASE

4503. Nearly all families preferred outpatient care, and few reported a loss of work hours or increased child care expenses. CONCLUSIONS Outpatient treatment of low-risk episodes of fever and neutropenia is substantially less costly than inpatient care and is preferred by most families.

Studies of the function and structure of in vitro propagated human granulocytes

The polymerase chain reaction (PCR) has been applied to detect occult leukemia cells in children with acute lymphoblastic leukemia who are otherwise considered in complete remission by traditional morphological examination of bone marrow specimens. To determine whether PCR provides unique prognostic information of use for the clinical investigator, we reviewed the 20 clinical studies published to date. From this review, it is evident that discrepancies exist for the detection of residual disease for patients who remain in complete remission and for those who relapse. However, because of the fundamentally different approaches used to apply the PCR method to each of these studies, an entirely different interpretation can be reached when critical technical factors are considered. The combined data from the various studies suggest that a consistent pattern for residual disease disappearance over many months exists for patients who remain in extended complete remission and a pattern of residual disease persistence and reappearance preceding clinical findings exists for the majority of those who ultimately relapse in the bone marrow.

Molecular genetic evidence for a differentiation-proliferation coupling during DMSO-induced myeloid maturation of HL-60 cells : role of the transcription elongation block in the C-MYC gene

In a patient with precursor B-cell acute lymphoblastic leukemia (ALL) associated with eosinophilia that completely responded to induction chemotherapy, we assayed serial remission cerebrospinal fluid and bone marrow specimens for minimal residual disease using a quantitative polymerase chain reaction assay to assess for clone-specific immunoglobulin heavy-chain gene cluster (IGH) gene rearrangement. Cerebrospinal fluid eosinophilia and minimal residual disease were detected on day 406, preceding the morphologic diagnosis of central nervous system relapse on day 578. By day 841, the bone marrow had 35% blasts. Despite aggressive therapy, including unrelated umbilical cord blood transplantation, the patient developed testicular and bone marrow relapses and died of disease. We conclude that increasing levels of minimal residual disease in cerebrospinal fluid can predict recurrence of ALL prior to clinical and morphologic relapse. Furthermore, we demonstrate a novel translocation in this tumor, the t(5;9)(q31;p24), that possibly led to fusion of the interleukin-3 (IL3) (5q31) and JAK2 (9p24) genes and may explain the concomitant appearance of eosinophilia and ALL.