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Purpose: Infection with human parvovirus B19 is the most common cause of transient aplastic crisis in patients with chronic hemolytic anemia. Multiple reports of children with simultaneous B19 infection and thrombocytopenia as well as the known association between experimental B19 infection and thrombocytopenia prompted us to hypothesize that B19 may be associated with childhood idiopathic, or immune, thrombocytopenic purpura (ITP). Because there is a paucity of evidence regarding a viral etiology for ITP, we performed a comprehensive study to explore its possible relationship to B19 infection., Patients and Methods: Thirty-five previously healthy children with ITP were studied prospectively. Bone marrow and peripheral blood were analyzed for B19 DNA using the polymerase chain reaction (PCR). Serum was analyzed for anti-B19 immunoglobulin (Ig) M and IgG antibodies using a B19 VP1 antigen-based enzyme-linked immunosorbent assay. Fourteen healthy children served as controls for peripheral blood PCR and serologic analyses., Results: The presenting clinical and laboratory features of the study population were typical of classic ITP. Seventeen of the 35 patients (49%) had evidence of B19 DNA in the peripheral blood, bone marrow, or both. Six of 35 (17%) had anti-B19 IgM antibodies. Eight of 35 (23%) were anti-B19 IgG seropositive. The control group had no positive PCR or anti-B19 IgM specimens., Conclusions: Our results suggest that infection with human parvovirus B19 may be associated with childhood ITP. More investigation is warranted regarding the role of PCR methodology and serologic detection methods in defining B19 pathobiology as it relates to ITP.

Purpose: Human B19 parvovirus infection may cause severe erythroid hypoplasia in patients with an underlying hemolytic anemia. We report a case of severe parvovirus-induced anemia with initial marrow erythroid hyperplasia in a child with no underlying hematologic disorder., Conclusions: The patient's rapid hemoglobin recovery after treatment with i.v. immunoglobulin further supports this form of therapy for children with parvovirus-induced anemia.

Giant hemangiomas occurring in the neonatal period often present a therapeutic challenge, especially when confounded by consumptive coagulopathy (Kasabach-Merritt syndrome). We treated three infants with tranexamic acid after therapy with corticosteroids was ineffective. One patient had a partial response. The remaining two developed progressive disease.

Autopsy specimens from a patient with infection-associated hemophagocytic syndrome (IAHS) were evaluated for the presence of Epstein-Barr virus DNA and RNA using in situ hybridization. Frozen sections of liver, lymph node, and spleen were probed with EBV Bam HI-H & W, gamma interferon, and SP-65 plasmid DNA as a negative control probe. Hybridization patterns before and after treatment with ribonuclease A were examined. Both EBV probes produced diffuse hybridization throughout the tissues; in addition, there were some foci of extremely heavy concentrations of silver granules. A gamma interferon probe showed evidence of hybridization, but the overall intensity was not as great as with EBV probes. Pretreatment with ribonuclease A dramatically decreased hybridization in all tissues to EBV probes, but hybridization with SP-65 was unaffected. The elimination of EBV hybridization with ribonuclease A pretreatment provides the first evidence of EBV gene expression in an IAHS patient.

The cases of 63 children treated for Hodgkin's disease were retrospectively evaluated according to clinical and laboratory characteristics at initial appearance, clinical and pathologic staging, and treatment for their effects on survival and disease-free survival. An initial erythrocyte sedimentation rate over 50 mm/h was common in patients who ultimately had a relapse. There was no correlation between the size of the mediastinal mass at diagnosis and occurrence of relapse. A residual mediastinal mass was found in 22% of patients after 1 year of treatment regardless of its size at initial appearance. With a median follow-up time of 10.5 years, the overall survival rate is 89%, and disease-free survival rate is 71%. The disease-free survival rates for patients with stages I-IV disease are 92, 81, 78, and 40%, respectively. Relapses occurred in 7 of 22 (36%) patients with positive staging laparotomy despite radiotherapy for three with stage IA and IIA disease, chemotherapy alone for two with stage IIIB disease, or chemotherapy for one with stage IIIB and one with stage IVB disease. Of patients who had no evidence of abdominal Hodgkin's disease at a staging laparotomy, 6 of 34 (19%) had a relapse. These included one with stage IA and five stage IIA disease, all treated with radiotherapy alone. Treatment of stage III and IV disease with regimens including CCNU (lomustine) or cyclophosphamide, plus vinblastine sulfate or vincristine sulfate, prednisone, and procarbazine hydrochloride with or without radiation therapy yielded poor results, with 6/7 having a relapse.

The virus-associated hemophagocytic syndrome (VAHS) is a histiocytic proliferative disorder with bone marrow and liver failure for which the connection with a specific virus is often tenuous. Epstein-Barr virus (EBV) is one candidate for the association, but serologic or culture confirmation may be lacking in a particular case. As a means of directly identifying the presence of EBV in patients' cells, molecular hybridization studies were carried out using a radioactively labeled viral DNA segment. DNA from mononuclear cells of two children with VAHS had specific hybridization to the EBV DNA probe. One of the patients had serologic evidence for EBV infection. Several immunologic deficiencies were found. VAHS may represent one of several hematologic and/or immunologic dysfunctions caused by EBV.

Nineteen children who presented with fever, hepato-splenomegaly, bone marrow and/or hepatic failure, and biopsy evidence of histiocytic proliferations were evaluated for lymphocyte dysfunction and evidence of prior viral infection. Seventeen of the children had erythrophagocytosis consistent with the previously described virus-associated hemophagocytosis syndrome (VAHS) or Familial erythrophagocytic lymphohistiocytosis (FEL). The other two had benign histiocytic proliferations in the central nervous system (CNS) with liver and bone marrow dysfunction. There were two sibling pairs and six patients with known disorders of immune deficiency. The remaining nine cases appeared to be sporadic and idiopathic. Epstein-Barr Virus (EBV) was identified in patients by serologic or DNA hybridization studies (15), EBV and cytomegalovirus (CMV) (1), adenovirus plus EBV and CMV (1), or adenovirus and EBV (1). Herpes zoster was associated with reactivation of symptoms in one patient. Immunologic impairment was evidenced by lymphopenia in 10 of 19 patients. More extensive evaluations could be done at diagnosis on only some of the children because the histiocytic proliferative syndrome was not recognized or because there were insufficient numbers of lymphocytes in samples obtained. For those who could be evaluated, the following immune deficiencies were found: decreased lymphocyte proliferation to mitogens (4 of 9), absent or markedly decreased natural killer function (5 of 5), and decreased cytotoxic lymphocyte reactivity to allogenic EBV-infected target cells (3 of 3). A new finding reported here is a higher than expected prevalence of HLA types A30, B8, and A1/B8 among the patients tested.

A 12-year-old white female with recurrent Burkitt's lymphoma had a spontaneous remission associated with a localized herpes zoster infection. The remission lasted nearly 2 months before the tumor recurred in the central nervous system. LDH isoenzyme determinations done on an earlier ovarian tumor and serum at time of bone marrow relapse showed different predominant LDH isoenzyme patterns. These data might be interpreted as showing that different malignant cell clones were responsible for ovarian and bone marrow relapses. Studies to elucidate the mechanism of spontaneous remission at the time of zoster infection demonstrated serum factor(s) which stimulated normal B lymphocytes.

We describe the development of Epstein-Barr-virus (EBV)-related lymphoproliferative disease (LPD) in the recipient of a histocompatible bone marrow transplant (BMT). Although this rare complication is more common in recipients of mismatched bone marrow, several distinguishing features of our case may have contributed to the development of LPD in the recipient of a matched bone marrow transplant. The patient had received marrow from a sibling with Trisomy 21, a syndrome associated with variable cellular and humoral immune defects. Our patient also was infected with cytomegalovirus and was treated with immunosuppressant therapy for graft versus host disease. Although development of LPD in transplant recipients is a multifactorial process, either acquired or congenital immunosuppression/dysregulation is a common prerequisite for the process. Our case suggests that subtle immune defects in individuals with Down syndrome may contribute to the immunosuppressed setting in which EBV-related LPD can develop.

A case of therapy-related myelodysplasia followed by acute nonlymphocytic leukemia in a 5-year-old child successfully treated for diffuse Langerhans cell histiocytosis is described. A syndrome of severe cell-mediated immune deficiency and persistent Epstein-Barr virus (EBV) infection coincided with the evolution of myelodysplasia. Specific abnormalities of chromosomes number 7 and 3 were associated with the onset of myelodysplasia and acute nonlymphocytic leukemia and are believed to be linked to the patient's immune dysfunction and compromised ability to contain viral infection.