Michael Rice

Childhood cancer: a 4-year prospective study of the psychological adjustment of children and parents.

PURPOSE The objective of this 4-year prospective study was to assess the psychological adjustment of children treated for cancer and their parents. PATIENTS AND METHODS Children aged 2 to 12 years with cancer diagnosed and their parents and families (n = 39) were assessed immediately after their diagnosis and then annually for the next 4 years. At each assessment, the psychological adjustment of the children and their families was compared with the adjustment of a cohort of children and families in the general community (n = 49). RESULTS Immediately after the diagnosis of cancer in the children, the children and their parents had significantly more psychological problems than children and parents in the community. However, at subsequent assessments, there was no difference in the number of psychological problems experienced by children and parents in the two groups. CONCLUSIONS In the longer term, the prevalence of psychological problems experienced by children treated for cancer and their parents does not differ from that found in children and parents in the general community. Future research should give greater attention to other aspects of the lives of children treated for cancer and their parents, including their broader health-related quality of life.

Childhood cancer : A two-year prospective study of the psychological adjustment of children and parents

OBJECTIVE To follow prospectively the psychological adjustment of young children, parents, and families during the first 2 years after the childrens diagnosis of cancer. METHOD Children aged 2 to 5 years with cancer diagnoses and their parents and families (n = 38) were assessed immediately after diagnosis, 1 year after diagnosis, and 2 years after diagnosis. At each assessment, the psychological adjustment of the children and their families was compared with the adjustment of a cohort of children and families in the general community (n = 39). RESULTS Children with cancer and their parents experienced significantly more emotional distress than children and parents in the community during the period immediately after diagnosis. However, the number of problems experienced by the children with cancer and their parents declined during the first year after the childrens diagnosis and stabilized at a level comparable with that found among children and parents in the general community. CONCLUSION Although the results are consistent with reports that suggest that in the longer term the prevalence of psychological problems among children with cancer is similar to that found among children in the general community, they also highlight the considerable distress experienced by children and parents during the period immediately after the childrens diagnosis.

IL-21 is the primary common γ chain-binding cytokine required for human B-cell differentiation in vivo

SCID resulting from mutations in IL2RG or JAK3 is characterized by lack of T and natural killer cells; B cells are present in normal number, but antibody responses are defective. Hematopoietic cell transplantation (HCT) is curative for SCID. However, B-cell dysfunction persists in a substantial proportion of patients. We hypothesized that impaired B-cell responses after HCT in IL2RG/JAK3 deficiency results from poor donor B-cell engraftment and defective γc-dependent cytokine signaling in host B cells. To test this, and to identify which γc cytokine(s) is critical for humoral immunity, we studied 28 transplanted patients with IL2RG/JAK3 deficiency. Lack of donor B-cell engraftment associated with persistent humoral dysfunction and significantly reduced memory B cells. B-cell proliferation induced by CD40L alone or together with CpG, anti-Ig, IL-4, IL-10, or IL-13 was comparable in healthy controls and in post-HCT SCID patients, irrespective of their chimerism status. However, in vitro stimulation with CD40L/IL-21 induced B-cell proliferation, plasmablast differentiation, and antibody secretion in patients with donor B cells, but not in patients with autologous B cells. These data imply that IL-21-mediated signaling is critical for long-lived humoral immunity and to restore antibody responses in IL2RG/JAK3-deficient patients after HCT. Furthermore, in vitro stimulation with CD40L/IL-21 can predict in vivo B-cell immunity in IL2RG/JAK3 SCID after transplantation.

A 3-year follow-up of the intellectual and academic functioning of children receiving central nervous system prophylactic chemotherapy for leukemia

This prospective study compared the intellectual and academic functioning of two groups of children treated for cancer over the 3 years after their diagnosis. One group consisted of children who received central nervous system (CNS) prophylactic chemotherapy, and the other group consisted of children with cancer who did not receive CNS chemotherapy. The results suggest that the children who received CNS chemotherapy experienced more adverse effects from their treatment in the area of academic functioning than the children who did not receive CNS chemotherapy. Although there were no differences in the academic, functioning of the two groups of children immediately after their diagnosis, 3 years postdiagnosis, the CNS-treated children scored more poorly on academic tests of reading, spelling, and arithmetic than the non-CNS-treated children. The results suggest that CNS chemotherapy prophylaxis may impede academic achievement.

A prospective study of the psychological adjustment of parents and families of children with cancer

This study compared the psychological adjustment of parents and families of children with cancer, with the adjustment of parents and families in the community. In the weeks after their childrens diagnoses, the mothers of children with cancer reported significantly more anxiety and insomnia, somatic symptoms and social dysfunction than mothers in the community. These problems had declined by the time of a 1 year follow‐up assessment However, at the follow‐up assessment the mothers of children with cancer reported significantly more symptoms of depression and somatic symptoms than mothers in the community. A similar pattern of findings was evident among the fathers although the fathers generally reported less distress than was reported by the mothers. The results also suggest that a year after the childrens diagnoses, the families in which there was a child with cancer were functioning less effectively than the families in the community.

Longitudinal follow-up of the intellectual and academic functioning of children receiving central nervous system-prophylactic chemotherapy for leukemia: a four-year final report.

This longitudinal investigation extends our prospective study of the intellectual and academic functioning of children treated for cancer to 4 years after diagnosis. In the longer term, the children who received central nervous system (CNS) chemotherapy experienced greater neurocognitive deficits, particularly in the area of academic achievement, than did the children who did not receive CNS chemotherapy. Specifically, the CNS chemotherapy-treated children scored lower on academic tests of reading at 3 and 4 years after diagnosis. The results suggest that CNS chemotherapy prophylaxis may adversely effect the development of higher-order mental abilities and cognitive skills during the late-effects period and may also impair academic achievement.

Renal toxicity after total body irradiation

Abstract Purpose: To evaluate the incidence of renal dysfunction after total body irradiation (TBI). Methods and Materials: Between 1990 and 1997, 64 patients (median age 50 years) received TBI as part of the conditioning regimen before bone marrow transplantation (BMT). Five patients with abnormal renal function at the beginning of treatment or with incomplete data were excluded. All patients received a total of 12 Gy (6 fractions twice daily for 3 consecutive days) prescribed to the peak lung dose (corrected for lung transmission) at a dose rate of 7.5 cGy/min. Renal shielding was not used. Renal dysfunction was assessed on the basis of the serum creatinine levels measured at the start and end of TBI and at 6, 12, 18, and 24 months after completion of BMT. Cox proportional hazard analysis was used to evaluate the various factors known to affect renal function. Results: Only 4 patients had elevated serum creatinine levels at 12 months and subsequently only 2 of the 33 surviving patients had persistent elevated renal serum creatinine levels 24 months after BMT. A fifth patient developed proteinuria and mildly elevated serum creatinine levels at 2.5 years. In 2 patients, the elevation coincided with disease relapse and normalized once remission was achieved. In the third patient, the elevation in serum creatinine levels coincided with relapse of multiple myeloma and the presence of Bence-Jones proteinuria. The fourth patient was the only patient who developed chronic renal failure secondary to radiation nephritis at 2 years. The etiology of the fifth patients rise in creatinine was unknown, but may have been secondary to radiation nephritis. On univariate analysis, but not on multivariate analysis, a significant correlation was found between TBI-related renal dysfunction and hypertension before and after BMT. Conclusion: A dose of 12 Gy at 2 Gy/fraction resulted in only 1 case of radiation nephritis in the 59 patients studied 24 months after the completion of TBI and BMT.

A prospective study of the psychological adjustment of children with cancer.

Purpose This paper describes the prevalence of emotional and behavioral problems and the social competencies of forty children with cancer immediately after their diagnosis and one year post-diagnosis. Patients and Methods At both points of time the problems and competencies of the children with cancer were compared with the problems and competencies of a matched group of children living in the community. Results The results suggest that early in their illnesses, younger children with cancer experience more internalising problems than children in the community. However, the younger children with cancer improved significantly in these areas during the year after their diagnosis. As a result, one year after their diagnosis there was little difference in the prevalence of problems amongst the younger children with cancer and the children in the community. The older children with cancer did not appear to have more problems than children in the community at either the first or the second assessment. Conclusions The results of the study draw attention to possible differences in the-prevalence of emotional and behavioral problems experienced by younger and older children with cancer. The results also suggest that amongst younger children with cancer the prevalence of problems declines during the year after their initial diagnoses.

Comparison of methods for assessment of minimal residual disease in childhood B-lineage acute lymphoblastic leukemia

The level of minimal residual disease (MRD) early in treatment of acute lymphoblastic leukemia (ALL) strongly predicts the risk of marrow relapse. As a variety of methods of varying complexity have been separately used for detecting and quantifying MRD, we compared the prognostic utility of three methods – measurement of blast percentage on day 14 of treatment, detection of monoclonality on day 14 or day 35, and measurement of MRD by PCR-based limiting dilution analysis on day 14 or day 35. The study group comprised 38 children aged 1–15 with Philadelphia-negative B-lineage ALL who were uniformly treated and followed until relapse or for a minimum of 5 years. We also studied some of the technical factors which influence the ability to detect MRD. Measurement of blast percentage on day 14 by an expert morphologist, detection of monoclonality on day 35, and PCR-based measurement of MRD levels on days 14 and 35 all showed significant ability to divide patients into prognostic groups. Measurement of blast percentage on day 14 by routine morphology or detection of monoclonality on day 14 were not useful. The quality of DNA samples varied greatly, as determined by amplifiability in the PCR. However, virtually all amplifiable leukemic targets in a sample were detectable which suggests that the level of detection achieved by limiting dilution analysis is essentially determined by the amount of DNA which it is practicable to study. We conclude that quantification of MRD at the end of induction provides the full range of prognostic information for marrow relapse but is complex; detection of monoclonality on day 35 is simple and has good positive predictive value; and quantification of MRD on day 14 merits further study. PCR-based methods for measurement of MRD levels should incorporate a correction for variation in DNA amplifiability.

Acute lymphoblastic leukemia characterized by t(8;14)(q11.2;q32)

The t(8;14)(q11.2;q32) is emerging as an uncommon, though recurrent cytogenetic finding. As of yet, too few cases of acute lymphoblastic leukemia (ALL) characterized by this translocation have been studied to determine its prognostic significance with confidence. We therefore report three new patients (two male children and one adult female) and present their hematologic, immunophenotypic, and clinical data. The clinical and laboratory characteristics of 26 other patients with t(8;14)(q11.2;q32) are summarized. The total number of patients now reported in the literature is 29 with a mean age of 14 years. Early relapse, that is, relapse within 6 months, does not appear to be a common feature of this group. The gender distribution is 19 males: 9 females (gender not reported in one case). Twenty-three t(8;14) patients show a pre-B immunophenotype and 24 of 24, on whom information is available, achieved complete remission after induction chemotherapy for B-ALL. Approximately one third of patients with t(8;14) have Down syndrome, 19 of 27 have additional acquired cytogenetic abnormalities, 5 of these have the t(9;22), and 4 show duplication of the abnormal chromosome 14, which is derived from the t(8;14). Hemoglobin and platelet counts are low at presentation in 10 of 10 and 8 of 9 patients, respectively, and the average white blood count is 38.9 x 10(9)/L. Of the 7 patients for whom IgH status has been determined, all show rearrangement of the IgH locus. Two of the present three patients are included in this group; their IgH rearrangement was demonstrated by fluorescence in situ hybridization with IgH break-apart probes.