Joseph D. Dickerman

The Late Effects of Childhood Cancer Therapy

In this article the difficulties that face survivors of childhood cancer therapy are presented, and the late effects of such therapy, separated into nonmalignant and malignant late effects, are discussed according to organ system. Recommendations for monitoring the late effects are set forth. A table listing radiation-therapy site and chemotherapeutic agents and selected late effects that result from their use is provided. Finally, a brief recommendation regarding the establishment of a late-effects clinic is also presented.

Intrathecal vincristine. Report of a fatal case despite CNS washout

The clinical course of a two‐year‐old girl with acute lymphocytic leukemia (ALL) who inadvertently received intrathecal vincristine is presented. Despite aggressive treatment with parenteral folinic acid and extensive central nervous system washout, the outcome was fatal. The pharmacologic aspects of vincristine and folinic acid that may explain why treatment was unsuccessful, are reviewed.

Pulmonary infection in splenectomized mice: Protection by splenic remnant☆☆☆

Our model of aerosol-induced pneumococcal pneumonia results in lung consolidation, sepsis, and death in mice depending upon the dose of organisms delivered; previous work has shown increased susceptibility in asplenic animals. These studies detailed the protection afforded groups of mice which retained half of their spleen. Male Swiss white mice were divided into three groups of splenectomized, sham-operated, and hemisplenectomized animals. Two weeks later they were exposed for 30 min to an aerosol producing a uniform challenge of 1010 Type III Streptococcus pneumoniae within a confined chamber. A second study was performed in which similar groups of animals were exposed to 109 organisms. At both bacterial dosage levels the splenectomized groups had significantly increased mortality (P < 0.001, P < 0.005) from pneumococcal disease; importantly, in both studies, each hemisplenectomized group did not differ from its control (sham-operated) group. We conclude that normal rates of protection from pneumococcal pneumonia are afforded animals which retain half of their splenic mass.

Slipped capital femoral epiphysis (SCFE) following pelvic irradiation for rhabdomyosarcoma

A 7‐year‐old child developed slipped capital femoral epiphysis (SCFE) 3 years following pelvic irradiation for rhabdomyosarcoma. The reasons for this occurrence are discussed. This is the second report of radiation‐induced SCFE and it is anticipated that more such cases are likely to occur. Cancer 44:480‐482, 1979.

Bleeding disorders in Noonan Syndrome

Noonan Syndrome (NS) is a common genetic disease with multiple organ defects including bleeding disorders, which was last reviewed in 1997. Since then significant information has been acquired regarding bleeding problems in NS, specifically on the underlying genetics. Associations between mutated genes and bleeding disorders are reviewed along with prevalence and underlying etiologies. Between 50–89% of NS patients will have a bleeding disorder and since a significant number will require surgery it is important to identify which ones are at risk prior to their procedure. Recommendations regarding screening for bleeding disorders and their treatment are discussed. Pediatr Blood Cancer 2012; 58: 167–172.

Interferon and Giant Cell Tumors

The article by Kaban et al1 appearing in this months issue of Pediatrics is of interest because it describes, to the best of my knowledge, the first completely successful medical treatment of a primary giant cell tumor of the bone with the angiogenesis inhibitor interferon α-2a. Previously, a 37-year-old woman with a benign giant cell tumor of the leg that spread to the lungs demonstrated a significant decrease in pulmonary metastases and stabilization of disease following treatment with interferon α-2a.2 Giant cell tumors of the bone have 3 major cell types: 1) proliferating mononuclear cells thought to be the neoplastic element of the tumor, 2) nonproliferating mononuclear cells, and 3) multinucleated giant cell that are fused mononuclear cells.3 The incidence of giant cell tumors among primary bone neoplasms is 4% to 5%, with most occurring around the knee and <1% in the skull. …

Lack of protection by pneumococcal vaccine after splenectomy in mice challenged with aerosolized pneumococci.

The efficacy of pneumococcal vaccine given after splenectomy lacks experimental validation. Adult CD-1 male mice that received type III pneumococcal capsular polysaccharide vaccine 1 microgram IP, 48 hours postsplenectomy and 7 days before challenge with aerosolized type III Streptococcus pneumoniae had a significantly higher mortality (96%) compared to immunized controls (64%) (p less than 0.002). The vaccine protected immunized sham-operated mice compared to unimmunized controls (p less than 0.015). Mice immunized 7 days before splenectomy were equally protected when compared to immunized sham-operated mice (p = NS). All deaths were secondary to culture-proven pneumococcal infection. These findings corroborate previous experimental and clinical studies demonstrating an impaired immunologic response and increased susceptibility to infection in asplenic individuals. Pneumococcal vaccines should be given before nonemergent splenectomy. Alternatives to splenectomy should be considered for patients with traumatized spleens where possible.

Fragile X syndrome and acute lymphoblastic leukemia

Fragile X (Fra(X) syndrome is an example of a heritable fragility syndrome associated with mental retardation. It is characterized by a fragile site on the X chromosome at Xq27–28. There have recently been three reports of malignant solid tumors associated with Fra(X) syndrome. We describe the first case of a hematologic malignancy [T‐cell acute lymphocytic leukemia (ALL)] in a patient with Fra(X) syndrome. The possibility of a predisposition to malignancy in Fra(X) is discussed.

Adrenal hemorrhage in the newborn. The phenomenon of "enclosed" hemorrhage as a cause of neonatal jaundice and later adrenal calcifications.

In an infant with unexplained hyperbilirubinemia, abdominal mass and a fall in hematocrit, an IVP with total body opacification should be considered so that the diagnosis of adrenal hemorrhage, which is almost always a benign conditions, may be made. Follow-up abdominal films at 3 months of age may further substantiate the etiology by revealing calcifications in the involved areas.

8;14 chromosome translocation in a negative bone marrow aspirate from a patient with Burkitt's lymphoma

A patient with Burkitts lymphoma is described who, on presentation, had a bone marrow aspirate which did not show abnormal cells. Cells from the bone marrow were cultured and an 8;14 chromosome translocation was identified. This finding allowed us to upgrade the stage of disease from III to IV with therapeutic as well as prognostic implications.