Acute allergic reaction due to milk proteins contaminating lactose added to corticosteroid for injection.

We encountered two patients with severe cow's milk allergy who reacted strongly to an injection of methylprednisolone sodium succinate (Sol-Medrol 40 mg Pfizer, Japan). They came to our hospital because of an asthmatic attack or urticaria and were treated with Sol-Medrol 40 mg. After the injection, the allergic reaction was immediate. Skin prick tests demonstrated that the beta-lactoglobulin contaminating the lactose of the drug preparation caused the immediate allergic reaction.

Long-term follow-up of busulfan, etoposide, and nimustine hydrochloride (ACNU) or melphalan as conditioning regimens for childhood acute leukemia and lymphoma.

We retrospectively evaluated early and long-term complications of an intensified conditioning regimen consisting of busulfan and etoposide in combination with either nimustine hydrochloride (ACNU) (BVA regimen, n = 18) or melphalan (BVL regimen, n = 34) in 52 children with acute leukemia or non-Hodgkin's lymphoma. With a median follow-up of 13.2 years after the BVA regimen and 8.1 years after the BVL regimen, 61% and 76% of patients, respectively, are in continuous complete remission. Transplantation-related mortality was 17% and 6% after the BVA and BVL regimens, respectively, and the corresponding relapse rates were 17% and 15%. The most common and severe toxicity was pulmonary complication in the BVA regimen, which was seen in 67% of patients and was life-threatening in 20%. Thirty-three percent of patients after the BVA regimen and 24% after BVL died of relapse or disease progression (n = 9), interstitial pneumonia (n = 2), fungal pneumonia (n = 1), or chronic graft-versus-host disease (n = 2). One of the long-term survivors developed secondary leukemia. A significant decrease in the height standard deviation score of more than 2 SD from diagnosis to the last follow-up was seen in 17% of the patients, with hypothyroidism in 15%, and alopecia in 42%. Because our experience is limited to a small heterogeneous population of patients who mainly underwent transplantation in the first remission, we cannot draw conclusions on the treatment's effectiveness. The BVL regimen is tolerable, however, because no regimen-related death was observed, whereas the BVA regimen is not recommended because of the high incidence of pulmonary complications. The effectiveness of the BVL regimen requires further study.

Neonatal periventricular leukomalacia due to severe, poorly controlled asthma in the mother.

BACKGROUND: We report a neonatal case of cystic periventricular leukomalacia (PVL) in which the hypoxia was considered to have been caused by severe asthma in the mother, who had not taken any medication during pregnancy because she was anxious about its possible effects on her unborn child. METHODS: After the mother had severe exacerbation of asthma for five days, the baby was born at 36 weeks in gestation, weighing 2100 g, and with moderate asphyxia. Although the baby had been aggressively treated in a neonatal intensive care unit, at birth, an ischemic area had been formed in the periventricular areas in the brain echogram. We suspected that she had severe brain damage due to prenatal hypoxia. RESULTS: The baby was found to have cystic PVL by ultrasonography at age 15 days, and diplegia at age 4 months. CONCLUSIONS: The poorly controlled, persistent and severe asthma of the mother may have caused prenatal hypoxia, resulting in the cystic PVL and lower limb palsy. Pregnant patients with poorly controlled asthma should be advised of the great risk of this condition to the fetus. Also, patients should be assured of the safety of modern asthma treatments.

Double allogeneic peripheral blood stem cell transplantation in a 9-year-old patient with relapsed acute lymphoblastic leukemia: case report.

A 9-year-old female patient with relapsed leukemia that was refractory to conventional reinduction chemotherapy was successfully treated with double allogeneic peripheral blood stem cell transplantation. The conditioning regimen for the first transplantation consisted of busulfan, etoposide, and melphalan, and that for the second transplantation was total body irradiation and thiotepa. Neither severe regimen-related toxicity nor graft-versus-host disease was observed. The patient is in complete remission without major complications for 5 years. Double transplantation should be considered as one of the possible treatments for refractory acute lymphoblastic leukemia.

Regulation of annexin II by cytokine-initiated signaling pathways and E2A-HLF oncoprotein.

In pro-B cell acute lymphoblastic leukemia (ALL), expression of the E2A-HLF fusion gene as a result of t(17;19)(q22;p13) is associated with poor prognosis, hypercalcemia, and hemorrhagic complications. We previously reported that the E2A-HLF fusion protein protects interleukin-3 (IL-3)-dependent lymphoid cells from apoptosis caused by cytokine starvation. Here, we report that annexin II, a surface phospholipid-binding protein and one of the proposed causes of the hemorrhagic complications of acute promyelocytic leukemia (APL), is also implicated in t(17;19)+ ALL. Annexin II was expressed at high levels in APL cells and in each of 4 t(17;19)+ leukemia cell lines, and annexin II expression was induced by enforced expression of E2A-HLF in leukemia cells. In IL-3-dependent cells, we found that annexin II expression was regulated by IL-3 mainly by Ras pathways, including Ras/phosphatidylinositol 3-kinase pathways. Moreover, E2A-HLF increased annexin II expression in IL-3-dependent cells in the absence of the cytokine. These findings indicate that E2A-HLF induces annexin II by substituting for cytokines that activate downstream pathways of Ras.

Low natural killer activity and central nervous system disease as a high-risk prognostic indicator in young patients with hemophagocytic lymphohistiocytosis.

BACKGROUND: Familial hemophagocytic lymphohistiocytosis HLH (FHL) is fatal, unless patients are rescued with hematopoietic stem cell transplantation (SCT). Although the molecular identification of FHL now is possible at least in part from perforin gene study, many cases escape detection or never are tested due to the lack of specific hallmarks, making diagnosis difficult. To the authors' knowledge, it remains to be determined whether persistently low natural killer cell (NK) activity and a high incidence of central nervous system (CNS) disease increase the probability of FHL. METHODS: The authors analyzed 42 HLH patients age < 2 years, 13 of whom developed overt CNS disease and 5 of whom demonstrated persistently deficient NK activity (Group 1). The remaining 24 patients had no CNS disease and had NK activity of moderate decrease to within the normal range (Group 2). RESULTS: In Group 1, CNS symptoms were detected in 6 cases within 1 month and between 4.5-9 months in 6 other patients. In these cases, spotty lesions demonstrating a high T2 signal in the white matter were noted on brain magnetic resonance imaging. The survival was significantly poor for patients in Group 1 unless they were rescued with SCT, which was performed in 5 of the 13 patients with CNS disease and in all 5 patients with persistent NK activity deficiency. SCT was successful in 9 patients, with no CNS sequelae reported after the transplantation. Conversely, the prognosis of the 24 patients in Group 2 was better and only 1 patient required SCT. CONCLUSIONS: Very young HLH patients (age < 2 years) who are at high risk of fatal FHL with persistently deficient NK activity and/or overt CNS disease require appropriate SCT to reverse CNS disease and achieve a complete cure.