Paucity of leukemic progenitor cells in the bone marrow of pediatric B-lineage acute lymphoblastic leukemia patients with an isolated extramedullary first relapse.

Isolated extramedullary relapse in childhood acute lymphoblastic leukemia (ALL) may be accompanied by occult bone marrow disease. We used a highly sensitive assay to quantify leukemic progenitor cells (LPCs) in the bone marrow of such patients. Multiparameter flow cytometry and blast colony assays were used to detect LPCs in the bone marrow of 31 pediatric B-lineage ALL patients with an isolated extramedullary first relapse. Sites of relapse were central nervous system (22 patients), testes (7 patients), and eye (2 patients). Bone marrow (BM) LPC counts ranged from 0/10(6) mononuclear cells (MNCs) to 356/10(6) MNCs (mean +/- SE, 27.8+/-13.1/10(6) MNCs). LPCs were undetectable in 19 patients (61%). The BM LPC burden at the time of extramedullary relapse was similar, regardless of site (Wilcoxon P = 0.77) or time of relapse (Wilcoxon P = 0.80). Compared with higher risk, standard risk at initial diagnosis showed a trend for increased BM LPC burden (mean +/- SE, 44.6+/-17.1 versus 7.5+/-3.3; Wilcoxon P = 0.22). After successful postrelapse induction chemotherapy, LPC counts in 21 evaluated patients ranged from 0/10(6) to 175/10(6) MNCs (mean +/- SE, 15.9+/-9.6/10(6) MNCs). By comparison, LPC burden was higher after successful induction chemotherapy among children with an early BM relapse (range, 0 to 3262/ 106 MNC; mean +/- SE, 166+/-107; Wilcoxon P = 0.11). Thus, not all patients with an extramedullary relapse have occult systemic failure with substantial involvement of the bone marrow, and after reinduction therapy, LPC counts were lower in these patients than in patients treated for an overt BM first relapse.

Natural killer-like T-cell lymphoma in the small intestine of a child without evidence of enteropathy.

A previously healthy 6-year-old boy developed symptoms of small intestinal obstruction and was found to have a large intraabdominal mass. At laparotomy the mass involved the jejunum and adjacent mesenteric lymph nodes, requiring resection. Microscopic and immunohistochemical studies demonstrated a T-cell non-Hodgkin's lymphoma, confirmed by finding clonal T-cell receptor-beta and -gamma gene rearrangements by Southern blot analysis. The immunophenotype of this lymphoma-CD3+CD4-CD8-CD56+TIA-1+ beta F1(-)-suggests that the tumor cells are cytotoxic natural killer (NK)-like T cells, probably of CD3+CD4-CD8- intraepithelial cell origin. Examination of the adjacent and distal small intestinal mucosa failed to show any significant pathologic change. This case was unusual because intestinal lymphomas in children are usually of B-cell origin and most commonly have small noncleaved cell morphology. Childhood intestinal T-cell lymphomas have not been the focus of specific study but appear to be rare. In adults, intestinal T-cell lymphomas often arise in the background of gluten-sensitive enteropathy (celiac disease). In contrast, this child had peripheral T-cell lymphoma, with NK-like T-cell features, in the small intestine with no clinical or histologic evidence of enteropathy.

Deletion (11)(q14.1q21).

We report on a 4-year-old girl with moderate developmental delay, horseshoe kidney, bilateral duplication of the ureters with right upper pole obstruction, hydronephrosis and nonfunction, and subsequent Wilms tumor of the right lower pole. She had an interstitial deletion of the long arm of chromosome 11 involving the region 11(q14.1q21).

Primary pericardial sarcoma in a neonate.

A 9-day-old infant was found to have an undifferentiated pericardial sarcoma. Despite intensive surgery and chemotherapy, the child died of progressive disease. This is the first report to our knowledge of a primary pericardial sarcoma in a newborn.

Heparin-induced thrombocytopenia: a prospective study.

Thrombocytopenia is a well-described complication of heparin therapy. Few studies describe the incidence of thrombocytopenia when low-dose heparin (10,000-15,000 units/day) is used for prophylaxis of deep venous thrombosis. In our study, ten of 66 courses (15%) of heparin prophylaxis in coronary care unit patients were accompanied by a mild thrombocytopenia with platelet counts below 150 X 10(3)/mm3. In all cases the platelet count returned to normal despite continued heparin therapy. Patients who became thrombocytopenic had significantly lower initial platelet counts. No cases of severe thrombocytopenia were seen (platelet count below 100 X 10(3)/mm3). No patient developed thrombosis, bleeding or elevated fibrin split products. Mild thrombocytopenia occurring after 2-5 days of low-dose heparin is common, but clinically insignificant.

Immunologic studies of three family members with the immunodeficiency with hyper-IgM syndrome.

We report the results of immunologic studies in a family in which the father (III-5) and his two daughters (IV-7 and IV-8) had the hyper-IgM syndrome (IHIS). Repeated immunoglobulin levels done on III-5 showed a typical IHIS pattern: low IgG, traces of IgA, and high IgM. IV-7, who also had stage IIA Hodgkin's disease, had a similar pattern except after irradiation therapy to sites of disease, when IgM dropped to normal range while IgG and IgA remained low. IV-8, on the other hand, had normal IgG and IgA and moderately elevated IgM until age 18 months, when she gradually developed the IHIS pattern. All three patients had normal numbers of B cells (sIg) and of T cells, although IV-7 had increased suppression. Finally, all three patients shared the A3,B7 haplotype and none was blood type O. IHIS is not necessarily X linked, is not associated with blood type O, and appears to be heterogeneous even within the same family. Inheritance in this family is apparently autosomal dominant and the father may represent a new mutation.

The myeloproliferative reaction in a child with Down syndrome: cytological and chromosomal evidence for a transient leukemia.

Infants with Down syndrome occasionally develop marked myeloproliferative reactions (MPR) indistinguishable from acute myelocytic leukemia but which spontaneously regress. Most authors have attributed MPR to immature or defective control on bone marrow development. In this report serial cytomorphologic and chromosomal findings in the bone marrow and peripheral blood of a child with the MPR suggests that MPR may be due to a spontaneously regressing clone of malignant cells. At the height of the myeloproliferative response, chromosomal studies demonstrated a clone of blast-like cells with a 21-22 translocation consistent with Down Syndrome and an X-8 translocation which was present only in the initial peripheral blood analysis harvested at 24 hours but was not present in the 72 hours samples. This X-8 translocation was not demonstrated in bone marrow or peripheral blood samples obtained at random times throughout the one year followup. During this period there was complete resolution of the MPR. In addition the chromosomes from one cell demonstrated several double minutes at the time of the MPR. Double minutes have previously been reported only in malignant diseases, especially tumors of neural origin and leukemia. These findings raise questions about the benign origin of the MPR and support the idea the MPR may be the result of a spontaneously regressing clone of malignant cells.

Aplastic anemia complicating infectious mononucleosis: a case report and review of the literature.

A 12 1/2-year-old white girl developed pancytopenia and severe aplastic anemia three weeks following symptoms of infectious mononucleosis. Pancytopenia complicating infectious mononucleosis has been reported in only nine previous cases and only three were proven to have aplastic anemia. The mean time from onset of symptoms of infectious mononucleosis to the nadir of pancytopenia was 21.3 days with a range of seven to 49 days. Two patients died from complications of the pancytopenia. In those patients who recovered, the mean time from diagnosis of the pancytopenia to recovery of bone marrow function was 6.25 days with a range of four to eight days. In contrast to other causes of aplastic anemia, return of normal platelet levels coincided with recovery from pancytopenia. The etiology of the pancytopenia and aplastic anemia are unknown but immunologic causes are suspected because of the rapid recovery of the bone marrow and its possible responsiveness to steroids.