Long-term outcome of children with acute promyelocytic leukemia: a randomized study of oral versus intravenous arsenic by SCCLG-APL group.

Realgar-Indigo naturalis formula (RIF), an oral traditional Chinese medicine mainly containing Realgar (As4S4), is highly effective in treating adult acute promyelocytic leukemia (APL). However, the treatment efficacy and safety of RIF have not been verified in pediatric patients. SCCLG-APL group conducted a multicenter randomized non-inferiority trial to determine whether intravenous arsenic trioxide (ATO) can be substituted by oral RIF in treating pediatric APL. Of 176 eligible patients enrolled, 91 and 85 were randomized to ATO and RIF groups, respectively. Patients were treated with the risk-adapted protocol. Induction, consolidation, and 96-week maintenance treatment contained all-trans-retinoic acid and low-intensity chemotherapy, and either ATO or RIF. The primary endpoint was 5-year event-free survival (EFS). The secondary endpoints were adverse events and hospital days. After a median 6-year follow-up, the 5-year EFS was 97.6% in both groups. However, the RIF group had significantly shorter hospital stays and lower incidence of infection and tended to have less cardiac toxicity. All 4 relapses occurred within 1.5 years after completion of maintenance therapy. No long-term arsenic retentions were observed in either group. Substituting oral RIF for ATO maintains treatment efficacy while reducing hospitalization and adverse events in treating pediatric APL patients, which may be a future treatment strategy for APL.

[Clinical and gene research of X-linked lymphoproliferative disease in a Chinese family].

OBJECTIVE: To verify the pathogenesis in Chinese and to investigate the genetic rule of X-linked lymphoproliferative disease (XLP) therein. METHODS: The case history of a proband of XLP, male, aged 1 year and 5 months, who died 40 days after hospitalization, was reviewed. Fourteen his family members were interviewed for the development history, anamnesis, and underwent physical examination. Single-strand conformation polymorphism (SSCP-PCR) and sequencing were used to detect the SH2D1A mutation among the elder sister, younger brother, and parents of the poband. RESULTS: The proband and his elder brother suffered with virus-associated hemophagocytic syndrome and both died in 40 days after the disease coming on in the last two years in succession. The second exon of SH2D1A of the younger brother of the proband showed a nonsense mutation in SH2D1A gene: the C-T nucleotide substitution at nucleotide position 462 result in a stop codon and pre-mature termination of protein synthesis. The mother was proved as mutation heterozygote of the C and T nucleotide on the same site. The other members of the family were proved normal. The clinical manifestation of the younger brother of the proband was Langerhans cell histiocytosis. CONCLUSION: Langerhans cell histiocytosis may be a new clinical phenotype of XLP. The gene of SH2D1A is responsible for the disease of XLP in Chinese too. The newly developed method of SH2D1A mutation analysis may be suitable in the diagnosis of XLP in Chinese.

[Treatment of thalassemia major with unrelated donor bone marrow transplantation].

OBJECTIVE: Allogeneic marrow transplantation is a curative therapy for thalassemia, but no more than 30% of patients have HLA-indentical sibling marrow donor. The selection of alternative donors of unrelative marrow and the study on the probability of treating thalassemia major with unrelated donor bone marrow transplantation are of importance. METHODS: Nine children with thalassemia were included in the study, and their gene mutational type were homozygote of thalassemia and double heterozygote, respectively. All of them were finally diagnosed of thalassemia major, and treated with unrelated donor bone marrow transplantation. To high-resolution HLA typing, two patients were matched, five had one unmatched isoform and two had two unmatched isoforms. The erythrocyte blood type was not matched in six patients. The preparative regimen included busulfan (oral use, 16 mg/kg, divided for 4 days), cyclophosphamide (intravenous use, 200 mg/kg, divided for 4 days), antithymocyte immunoglobulin (intravenous use, 30 mg/kg, divided for 3 days), and fludarabine (intravenous use, 125 mg/m(2), divided for 3 days). Ciclosporin A and methotrexate were used for graft-versus-host disease (GVHD) prophylaxis. RESULTS: All patients had allergen reactions. One had hypotension. Five patients experienced I degrees approximately III degrees acute GVHD in the skin, while one had II degrees acute GVHD in liver. One patient had III degrees GVHD of intestines and gradually developed chronic GVHD in the skin, lungs and brain. One patient died of pulmonary hemorrhage. The duration when peripheral blood neutrophil count exceeded 0.5 x 10(9)/L was 12 - 26 days. The recovery time of WBC was as long as 23 - 110 days. Thrombocytes exceeded 50 x 10(9) within 61 approximately 142 days. The time when hemoglobin reached 100 g/L varied from 23 to 116 days. The last blood transfusion was on 13 - 62 days. Eight patients were fully grafted, while one was not grafted. During the 6 - 24 months of follow-up, seven patients' genotype of thalassemia major became normal. The erythrocyte blood type of five patients also changed into the same as that of donor. The hemoglobin was kept over 110 g/L without blood transfusion. CONCLUSION: The transplantation of unrelated donor bone marrow for thalassemia major was successful. Unrelated donor bone marrow transplantation could cure thalassemia major, which expanded the marrow donor source for the transplantation of thalassemia major.

[Expression and purification of telomerase resever transcriptase motifs in E.coli].

Our project is designed to clone a 1.3kb gene fragment of telomerase catalytic subunit gene which contains seven reverse transcriptase motifs and specific region with conserved sequence termed "T motif". The gene fragment was amplified by PCR and was inserted into expression vector pET28-b. The recombinant plasmid was induced by IPTG for 4h and a 52KD recombinant protein was produced. Amount of hTRT recombinant protein expression was 20% of total bacterial protein in the form of inclusion. Inclusion was dissolved in 8 mol/L urea and 10 mmol/L DTT and carried out affinity purification under denaturing condition. The purified hTRT recombinant protein was conformed by Western-blot successfully.