Impact of immunosuppression intensified conditioning regimen for patients with strong positive pre-transplantation donor-specific anti-HLA antibodies (DSAs) undergoing haploidentical hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To explore the efficacy of immunosuppression intensified conditioning regimen in patients who have strongly positive donor-specific Anti-HLA antibodies (DSAs) and received a haploidentical hematopoietic stem cell transplantation (haplo-HSCT) . Methods: Clinical data of 10 patients with strongly positive pretransplant DSAs (defined as MFI ≥10000) were retrospectively analyzed in this study. All of them received a haplo-HSCT in the Hematology Department of Shanghai Zhaxin Traditional Chinese & Western Medicine Hospital. Results: ① Of all ten patients, three were males, and seven were females, with a median age of 53.5 (36-64) years. Of the 10 patients, three were diagnosed with acute myeloid leukemia, two were myelodysplastic syndromes (MDS), two were chronic myelomonocytic leukemia (CMML), two were in an accelerated phase of chronic myeloid leukemia (CML-AP), and one was primary myelofibrosis (PMF). ② Conditioning regimen consisted of fludarabine (Flu) /busulfan (Bu) combined with whole-body irradiation (TBI) /cyclophosphamide (Cy). ③ On the seventh day after transplantation, the median pretransplant DSA level was MFI 15 999 (10 210-23 417) and 10 787 (0-22 720). ④ Eight patients acquired hematopoietic reconstitution; the median time of neutrophil engraftment was 14 (10-16) days; and 18 (14-20) days for platelet engraftment. After a median follow-up of 12.5 (1.5-27) months, primary graft failure was found in one patient and another with poor graft function. Seven patients remained in a disease remission state, and all were DSA-negative. Conclusions: An intensified immunosuppression conditioning regimen can efficiently decrease the level of donor-specific anti-HLA antibodies (DSAs), leading to good short-term efficacy.

Clinical significance of dynamic monitoring of cell chimerism following allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the relationship of chimerism status of cell subsets with engraftment, occurrence of acute graft versus host disease (aGVHD), graft rejection and disease relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>Chimerism status in peripheral blood (PB) and bone marrow (BM) of 65 patients received allo-HSCT were monitored at regular intervals post-transplant. Fluorescence-activated cell sorter (FACS) was used to sort CD3(+)T lymphocytes in 65 cases, CD3(-)CD56(+)CD16(+)NK cells in 52 cases, CD15(+) granulocytes in 32 cases and CD19(+)B lymphocytes in 20 cases post transplants. The chimerism status of different lineage cells was analyzed by polymerase chain reaction amplification of short tandem repeats (PCR-STR).</p><p><b>RESULTS</b>On day +7, NK-cells donor chimerism (DC 55.5%) was higher than other cell subsets. T lymphocyte was the latest one to reach complete donor chimerism (CDC) with a median on day +21. Patients whose T lymphocytes donor chimerism was more than 70% on day +7 and more than 95% on day +14 had a high risk for acute aGVHD. In all cases except those with ALL, the decreased DC of T lymphocytes were observed before molecular or hematological relapse occurred.</p><p><b>CONCLUSION</b>Serial and quantitative T cell chimerism analysis provides a reliable and rapid screening method for the early detection of engraftment, graft rejection, disease relapse and occurrence of aGVHD, therefore, is a prognostic tool to identify patients at high risk of aGVHD and disease relapse following allo-HSCT.</p>

A modified cytogenetic study for multiple myeloma / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To evaluate the effect of modified culture method used to cytogenetic analysis and the clinically significance of chromosomal abnormalities to multiple myeloma (MM).</p><p><b>METHODS</b>Mononuclear cells were isolated from bone marrow aspirate of 20 MM patients; and then cultured for 3 days without any cytokines, and 6 days in the presence of IL-6 (10 ng/mL) and GM-CSF (30 ng/mL) before RHG banding analysis; the remained part of aspirates were treated directly. Eight cases of iron deficiency anemia were taken as control.</p><p><b>RESULTS</b>The experiment was failure in 2 cases because of blood clot, and another 2 cases could be analyzed only by direct method due to inadequate cells. The karyotype abnormalities were found from 4 cases of 16 available patients. Of them, three cases had complex karyotypes. The abnormalities were detected after 6 days culture with addition of cytokines. No abnormalities were detected from those groups of directly analysis and 3 day culture. Meantime, the clinical data showed that the patients with cytogenetic abnormalities were in stage III, and had a high percentage of MM cells (25%-56%) in their bone marrow, and also poor responses to prior chemotherapy. No cytogenetic abnormalities were found from control individuals in all groups.</p><p><b>CONCLUSION</b>Extended culture in the presence of cytokines could improve the efficiency of cytogenetic analysis to MM. Complex karyotype was common cytogenetic abnormalities in MM patients with poor response to chemotherapy.</p>

Effects of raloxifene hydrochloride on bone mineral density, bone metabolism and serum lipids in Chinese postmenopausal women with osteoporosis: a multi-center, randomized, placebo-controlled clinical trial / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Raloxifene has been approved for prevention and treatment of postmenopausal osteoporosis in Caucasian women. It also has some positive effects on serum lipids in Caucasians. The objective of this study was to determine the effect of raloxifene hydrochloride on lumbar spine and total hip bone mineral density (BMD), bone metabolism, and serum lipids in Chinese postmenopausal women with osteoporosis.</p><p><b>METHODS</b>This was a multi-center, randomized, double-blind, placebo-controlled clinical trial in which 204 postmenopausal Chinese women with osteoporosis were assigned to receive raloxifene (60 mg) or placebo treatment daily for 12 months. BMD, serum bone metabolism markers, and serum lipids were measured before and after drug administration. BMD was measured by Dual-Energy X-Ray Absorptiometry (DEXA) and bone metabolism markers were analyzed by one-step enzyme-linked immunosorbent assay. Serum lipids were measured by enzymatic analysis.</p><p><b>RESULTS</b>At the end of the 12-month study, lumbar spine BMD increased in both groups with a mean increase of (3.3 +/- 4.8)% in the raloxifene group and (1.0 +/- 4.9)% in the placebo group (P < 0.001). There was a mean increase in total hip BMD of (1.4 +/- 4.8)% in the raloxifene group and a mean decrease of (0.9 +/- 5.0)% in the placebo group (P < 0.001). No subject in the raloxifene group had a new vertebral fracture and 5 placebo subjects had new fractures (P > 0.05). In the raloxifene group, the median decreases in the biochemical markers of bone metabolism serum osteocalcin and C-telopeptide were 41.7% and 61.5%, respectively. These changes were statistically significant compared with those in the placebo group (10.6% and 35.6%, P < 0.001, respectively). Both total cholesterol and low-density lipoprotein cholesterol decreased significantly in the raloxifene group compared with those in the placebo group (P < 0.001, respectively) and there was no significant effect of raloxifene on high-density lipoprotein cholesterol and triglycerides compared with placebo.</p><p><b>CONCLUSIONS</b>Raloxifene 60 mg/d for 12 months significantly increases lumbar spine and total hip BMD, significantly decreases bone turnover, and has favourable effects on serum lipids in Chinese postmenopausal women with osteoporosis.</p>