The effect of WT1 expression on the prognosis of allogeneic hematopoietic stem cell transplantation in acute leukemia / 中华血液学杂志

Objective: To study the effect of WT1 expression on the prognosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acute leukemia (AL) and its significance as molecular marker to dynamically monitor minimal residual disease (MRD) . Methods: Retrospectively analyzed those AL patients who underwent allo-HSCT in the First Hospital Affiliated to Zhejiang University School of Medicine during Jan 2016 to Dec 2017, a total number of 314 cases, 163 males and 151 females, median age was 30 (9-64) years old. Comparing the difference of WT1 expression at diagnosed, pre-HSCT and after HSCT. Using the receiver operating characteristic (ROC) curve to determine the WT1 threshold at different time so as to predict relapse. The threshold of WT1 expression before transplantation was 1.010%, within 3 months after HSCT was 0.079% and 6 months after HSCT was 0.375%. According to these thresholds, WT1 positive patients were divided into low expression groups and high expression groups. Analyzed the relationship between overall survival (OS) , disease-free survival (DFS) , cumulative incidence of relapse (CIR) and WT1 expression. Results: The OS and DFS of high expression group pre-HSCT were lower than low expression group [69.2% (9/13) vs 89.1% (57/64) , χ(2)=4.086, P=0.043; 53.8% (7/13) vs 87.5% (56/64) , χ(2)=9.766, P=0.002], CIR was higher than low expression group [30.8% (4/13) vs 7.8% (5/64) , P=0.017]. There was no significant difference of OS and DFS between high expression and low expression group of 3 months after HSCT (P=0.558, P=0.269) . The OS and DFS of high expression group of 6 months after transplantation were both lower than low expression group (P=0.049, P=0.035) . Multivariate analysis showed that WT1>0.375% when 6 months after transplantation was the only independent prognostic factor for shorter DFS (P=0.022) . There was no statistically significant difference in CIR between the high-expression group and the low-expression group 3 months after transplantation and 6 months after transplantation (P=0.114, P=0.306) . Conclusion: High expression of WT1 before and after HSCT was an adverse prognosis factor. It is of clinical practical value to use WT1 as a transplant recommendation index for patients with acute leukemia and as a marker to monitor MRD dynamically.

Candida tropicalis arthritis in a patient with acute leukemia / 中国实验血液学杂志

Candida arthritis in patient with hematological malignancy is rare. A case of Candida tropicalis arthritis of knee occurred in a patient with acute monocytic leukemia was reported during the recovery phase of post chemotherapy myelosuppression and agranulocytosis. The patient was diagnosed as Candida tropicalis arthritis of knee according to the Candida tropicalis isolated from the synovial fluid. Itraconazole and amphotericin B were intravenously injected for therapy for 4 - 5 weeks based on the susceptibility test in vitro, which showed better efficacy. But the arthritis relapsed at 4 - 6 weeks after the drug withdrawal. The curative effect was found in patient after treatment with fluconazole injection and articular cavity douching with amphotericin B for 8 weeks. In conclusion, although Candida arthritis in patient with hematological malignancy is rare, it still occurred in the patient with hypoimmunity. The treatment emphasis showed be placed on the full dosage and full treatment course of antifungal agent.

Study on unrelated donor allogeneic bone marrow transplantation with Bu-CY2 conditioning regimen for myelodysplastic syndrome / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of Bu-CY(2) conditioning regimen on allogeneic bone marrow transplantation (BMT) with unrelated donor for myelodysplastic syndrome.</p><p><b>METHODS</b>Six patients received chemotherapy regimen of busulfan (Bu) and cyclophosphamide (CY) before allogeneic BMT (Bu 4 mg . kg(-1) . d(-1), -7 d - -4 d, CY 60 mg . kg(-1) . d(-1), -3 d - -2 d). Mycophenolate mofetil combined with cyclosporin A and methotrexate was used for prevention of acute graft-versus-host disease after transplantation. Lipo prostaglandin E(1)was used in prophylactic regimen for hepatic veno-occlusive disease.</p><p><b>RESULT</b>Neutrophil count began to be higher than 0.5 x 10(9)/Lat the 18th day after BMT. Platelet count began to be higher than 20 x 10(9)/Lat the 21st day after BMT. Disease-free survival in the six patients was 27 months.</p><p><b>CONCLUSION</b>Bu-CY(2) conditioning regimen on allogeneic bone marrow transplantation with unrelated donor is an effective therapy for patients with myelodysplastic syndrome.</p>

Mycophenolic acid induced apoptosis in T lymphocytic cells Molt-4 and its mechanism / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To determine whether mycophenolic acid (MPA) exerts an apoptotic effect on human leukemic T cells Molt-4 and to elucidate its possible mechanism.</p><p><b>METHODS</b>Cell morphology, DNA fragmentation, cell cycle,percentage of annexin V positive cells and enzymatic activity of caspase-3 were measured by microscopic, electrophoretic and flow cytometric techniques respectively. Human leukemic B cell line Raji was used as control.</p><p><b>RESULT</b>MPA could induce apoptosis of Molt-4 cells with dose-and time-dependent manners; cells were blocked in the S phase. The activity of caspase-3 was enhanced in a dose-dependent manner in Molt-4 cells treated with MPA for 24 h. MPA could not induce apoptosis in Raji cells.</p><p><b>CONCLUSION</b>MPA can induce apoptosis in Molt-4 cells which may be involved in the activation of caspase-3.</p>

Treatment of childhood leukemia with unrelated donor allogeneic bone marrow transplantation / 中华儿科杂志

<p><b>OBJECTIVE</b>Allogeneic bone marrow transplantation has been established as a standard method for the treatment of a range of malignant and non-malignant hematologic diseases in children. Unfortunately, fewer than 30% of patients have a human leukocyte antigen (HLA)-matched sibling. Advances in our understanding of the HLA system and the development of large international donor registries encourage the increasing use of unrelated donors as an alternative source of stem cells. The purpose of this study was to evaluate the clinical efficacy and safety of unrelated donor allogeneic bone marrow transplantation (URD-BMT) for the treatment of childhood leukemia.</p><p><b>METHODS</b>Six patients with leukemia received URD-BMT. Two of them suffered from chronic myeloid leukemia (CML), 3 suffered from acute lymphocytic leukemia (ALL) and 1 suffered from acute promyelocytic leukemia (APL) (CR2). All cases were facilitated by Tzu Chi Marrow Donor Registry (TCTMDR). The high resolution DNA test for classIand II was carried out in HLA typing of all donor-receiver pairs. HLA allele matched in three cases, mismatched with one locus in two cases and with two loci in one case. All patients were prepared with cyclophosphamide (CY) 60 mg/kg/day for 2 days (total dose 120 mg/kg) and busulfan (Bu) 1 mg/kg x 4/day for 4 days (total dose 16 mg/kg). Mycophenolate mofetil (MMF), CsA and MTX were given to prevent acute graft-versus-host-disease (aGVHD). CsA of 3 mg/kg/d was continuously given by i.v. infusion, and then 6mg/kg/d by oral. The blood CsA concentration was 200 - 300 ng/ml. MTX was given at the dosage of 15 mg/m(2) on d 1 and 10 mg/m(2) on d 3, 6,9 or 11. MMF was given at the dosage of 0.25 - 0.5 g/d from day 0 to day 120. Prostaglandin E1 was given to prevent the hepatic veno-occlusive disease (VOD), Ganciclovir was used to prevent CMV infection until the CMV antigenemia became negative.</p><p><b>RESULTS</b>Analysis of DNA short tandem repeats showed total engraftment of donor marrow after transplantation in all cases. The median time when granulocyte exceeded 0.5 x 10(9)/L was 14.5 (13 - 18) days, platelets exceeded 20 x 10(9)/L was 16 (14 - 23) days. The acute GVHD grade II-IV occurred in 2 of 6 (33.3%) patients. There were 3 cases with chronic GVHD and none of them developed with the extensive chronic GVHD. All patients were alive in disease-free situation now with median follow-up 412 (187 - 1338) days.</p><p><b>CONCLUSION</b>URD-BMT is an effective method for the treatment of childhood leukemia.</p>

A comparison of clinical outcomes between HLA allele matched and 1 - 2 alleles mismatched unrelated allogeneic bone marrow transplantations / 中华血液学杂志

<p><b>OBJECTIVE</b>To compare the clinical outcomes between HLA allele matched (HLA-M) and 1 approximately 2 alleles disparity mismatched (HLA-mis) unrelated allogeneic bone marrow transplantation (URD-BMT).</p><p><b>METHODS</b>Thirty-nine patients received HLA-M and 21 received HLA-mis URD-BMT for the treatment of acute leukemia, chronic myeloid leukemia in chronic phase (CP) and myelodysplastic syndromes (MDS) in our hospital between November 1998 and December 2002. Conditioning regimen was Bu 16 mg/kg plus CTX 120 mg/kg, and mycophenolate mofetil (MMF), CsA and MTX were given to prevent aGVHD.</p><p><b>RESULTS</b>Thirty-eight of the HLA-M group and 18 of the HLA-mis group were engrafted successfully. The median follow-up duration was 11 (2.5 - 52.0) months for HLA-M group and 9 (2 - 46) months for HLA-mis group. The 3-year probabilities of disease-free survival (DFS) for HLA-M and HLA-mis group were (79.2 +/- 7.1)% and (45.8 +/- 15.5)%, respectively (P < 0.05). Grade II - IV aGVHD occurred in 10 (26.3%) patients in HLA-M group and 6 (33.3%) in HLA-mis group, respectively (P > 0.05).</p><p><b>CONCLUSION</b>URD-BMT is an effective modality for the treatment of leukemia and MDS. The outcome after URD-BMT can be optimized by matching the HLA-A, B and DR alleles between the donor and recipient.</p>