Summary:There exists limited information about the usefulness of hemopoietic stem cell transplantation (HSCT) for the treatment of patients with refractory Langerhans cell histiocytosis (LCH). We report here four Japanese pediatric patients with multisystem LCH disease who underwent HSCT between 1994 and 1997. Two of the four patients are doing well without any relapse. However, neither of them shows improved sequelae 3 to 4 years after allogeneic HSCT, although the graft was rejected in one of the cases. The remaining two patients died of septic shock. A review of the literature of 11 patients revealed four fatalities after the use of HSCT in the treatment of LCH. Three of these were due to active LCH and three deaths occurred within 2 months after HSCT. To establish the usefulness of HSCT for refractory LCH, further studies are required.

A high incidence of disseminated intravascular coagulation (DIC) in adult patients with acute lymphoblastic leukemia (ALL) is reported. However, studies comprising both childhood and adult patients are sparse and the clinical relevance of DIC in ALL patients has been a conflicting issue. Coagulation profiles at presentation and within seven days after starting remission-induction therapy of 44 childhood and 51 adult ALL patients were studied. At presentation, two childhood (5%) and 11 adult (22%) patients had DIC (p<0.05). After starting therapy, four of 27 childhood (15%) and 14 of 33 adult (42%) patients screened for coagulopathy developed DIC (p<0.05). Overall, six of the 44 children (14%) and 25 of the 51 adults (49%) were complicated with DIC (p<0.001). In the adult cases, DIC was more frequently complicated with FAB subtype L2 than L1 (p<0.05). All hemorrhages seen in the childhood cases were minor hemorrhages. In the adult patients, two patients with DIC had WHO grade 3 hemorrhage and the other hemorrhagic complications were minor hemorrhages. While milder induction therapies starting with corticosteroid given for childhood cases should be taken into consideration when comparing the incidences of DIC after therapy, the findings indicated that childhood and adult ALL may differ in the procoagulant characteristics. Morphological distinction between L1 and L2 appears to have relevance in the procoagulant activity in adult ALL. DIC complicating ALL is generally mild, however, sometimes causes severe hemorrhages in adults.

Non-T-cell-depleted HLA-haploidentical hematopoietic stem cell transplantation (SCT) from family members has been reported, but its effectiveness and safety are not fully known. In this study, we examined the outcomes of 83 children and adolescents with nonmalignant (n = 11) or malignant (n = 72) disorders who underwent SCT mismatched at 2 or 3 HLA loci, either from the mother (n = 56), a noninherited maternal antigen (NIMA)-mismatched sibling (n = 14), or the father/a noninherited paternal antigen (NIPA)-mismatched sibling (n = 13). Engraftment was satisfactory. Severe (grade III-IV) acute graft-versushost disease (GVHD) was noted only in malignant disease, with an incidence of 21 of 64 evaluable patients. GVHD prophylaxis with a combination of tacrolimus and methotrexate was significantly associated with a lower risk of severe acute GVHD, compared with other types of prophylaxis (P = .04). Nine of 11 patients with nonmalignant disease and 29 of 72 patients with malignant disease were alive at a median follow-up of 26 months (range, 4-57 months). Outcomes were not significantly different among the 3 donor groups (mother versus NIMA-mismatched sibling versus father/NIPA-mismatched sibling) for the malignancy disorders. Our results indicate that non-T-cell-depleted HLA-haploidentical SCT may be feasible, with appropriate GVHD prophylaxis, for young recipients who lack immediate access to a conventional stem cell source.

We studied changes in the drug sensitivity of clonogenic leukemic blast cells from patients with acute myeloblastic leukemia during clinical courses. These cells were assayed using the colony formation technique in methylcellulose culture. Various doses of each of two chemotherapeutic agents, daunorubicin and aclarubicin, were added at the start of culture, and drug sensitivities were measured in terms of percentage inhibition of leukemic blast colony formation. Clonogenic leukemic blast cells became less sensitive to the drugs which were administered to the patients during the course of the disease, suggesting that development of drug resistance in vivo may reflect the presence of dominant resistant populations of clonogenic leukemic blast cells in vitro.

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