Treatment responses of childhood aplastic anaemia with chromosomal aberrations at diagnosis.

The clinical outcome of childhood aplastic anaemia (AA) with aberrant cytogenetic clones at diagnosis was surveyed. Among 198 children with newly diagnosed AA registered with the AA Committee of the Japanese Society of Paediatric Hematology between 1994 and 1998, cytogenetic studies of bone marrow (BM) cells were completed in 159 patients. Apart from one Robertsonian translocation, seven patients (4.4%) showed clonal chromosomal abnormalities in hypoplastic BM without myelodysplastic features. The patients included six girls and one boy with a median age of 11 years (range 5-14 years). Six patients had del(6), del(5), del(13), del(20), or -7, and one showed add(9). Four patients responded to the first immunosuppressive therapy (IST: cyclosporin A plus anti-thymocyte globulin) and one obtained a spontaneous remission. Cytogenetic abnormalities remained in two patients with an IST response. On the other hand, two patients showed no IST response. One did not respond to repeat IST and died of acute graft-versus-host disease after an unrelated-BM transplant. Another obtained a complete response after a successful BM transplant. No haematological findings at diagnosis predicted the treatment response. No significant morphological changes developed during the course of the illness. A literature review revealed that half of 24 AA patients with chromosomal abnormalities responded to the first IST, and that +6 was the sole predictable marker for IST unresponsiveness. These results suggest that IST can be applied as the initial therapy for AA with cytogenetic abnormalities in the absence of completely matched donors.

Synergistic action of beta-glucan and platelets on interleukin-8 production by human peripheral blood leukocytes.

The effects of human platelets on interleukin (IL)-8 production from human peripheral blood mononuclear cells (PBMCs) and polymorphonuclear leukocytes (PMNs) stimulated with the fungal (1-->3)-beta-D-glucan schizophyllan (SPG) were examined using ELISA. PBMCs/PMNs in the presence of platelets and SPG enhanced IL-8 production in comparison with those in the presence of either platelets or SPG. IL-8 production was dependent on the concentration of platelets and incubation time, and the activity reached the maximal level at 18 h of incubation. These activities were also observed with the addition of platelets prestimulated with SPG to PBMCs. Addition of SPG directly enhanced expression of P-selectin on platelet membrane surfaces. These results suggest that platelets play a key role in the cytokine production of leukocytes induced by fungal (1-->3)-beta-D-glucans and might be mediated, at least in part, by P-selectin.