Control study of melphalan instead of cyclophosphamide as a myeloablative conditioning regimen for allogeneic hematopoietic stem cell transplantation for treatment of myeloid malignancies / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate melphalan instead of cyclophosphamide in modified busulfancyclophosphamide regimen as a new myeloablative conditioning regimen for the treatment of myeloid malignancies patients receiving allogeneic hematopoietic stem cell transplantation （HSCT）.</p><p><b>METHODS</b>The clinic data of 94 myeloid malignancies patients undergoing allogeneic HSCT were analyzed, of which 48 patients received Bu+Cy+Flu+Ara-C, 46 cases Bu+Mel+Flu+Ara-C regimens. Rregimen-related toxicity, engraftment, graft- versus-host disease（GVHD）, infection condition, non- relapse mortality, and overall survival were compared between the two groups.</p><p><b>RESULTS</b>All patients achieved neutrophil engraftment. The incidence of grade Ⅲ-Ⅳ oral mucositis and diarrhea in BMFA group was higher than in BCFA group（P<0.05）. The incidence of acute GVHD in BMFA group was also higher than in BCFA group but without statistically significant difference（36.5% over 56.5%, P=0.100）. With a median follow up of 42 months, the incidence of no relapse mortality in BCFA group was 12.5% and 19.6% in BMFA group（P=0.400）. The relapse rate in BMFA group（4.3%）was significantly lower than in BCFA group （25.0%, P=0.009）. The overall survival rates were（71.8±6.7）% and（76.1±6.3）%（P=0.852）, and diseasefree survival rates were（67.8±8.9）% and（76.1±6.3）%（P=0.567）were comparable between BCFA group and BMFA group.</p><p><b>CONCLUSION</b>Melphalan instead of cyclophosphamide as a new myeloablative conditioning regimen had lower relapse and satisfied disease-free survival rates, but the risk of regimenrelated toxicity and GVHD should be taken into consideration.</p>

IL-18 single nucleotide polymorphisms in hematologic malignancies with HLA matched sibling donor allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the impact of interleukin-18 (IL-18) single nucleotide polymorphisms on outcomes of hematologic malignancies with HLA-matched sibling donor hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>Single- nucleotide polymorphisms in IL-18 promoter was detected by PCR-sequence-specific primer analysis (PCR-SSP) in 93 recipients and their HLA matched sibling donors. Hematopoietic reconstitution, incidences of graft versus host disease (GVHD) and infections, transplant related mortality (TRM), and disease free survival (DFS) were analyzed.</p><p><b>RESULTS</b>In comparison with -137 G/C+C/C donor genotype, patients with -137 G/G donor genotype had shorter duration of neutrophil recovery [15(11-23) days vs 17(11-24) days, P=0.01], higher incidence of extensive chronic GVHD (20.6% vs 3.3%, P=0.029), but no difference in the interval of platelet recovery [20(11-46) days vs 20(7-38) days, P=0.844]. The incidence of extensive chronic GVHD in -607 C/C donor genotype (31.6%) was significantly higher than that (10.8%) in C/A + A/A donor genotype (P=0.024). Recipients with -607 C/C genotype also had higher incidence (33.3%) of extensive chronic GVHD than those with C/A+A/A genotype (10.7%, P=0.016). There were no differences in acute GVHD, TRM, and DFS between different genotypes.</p><p><b>CONCLUSION</b>IL-18 -137 G homozygous genotype in donor facilitated neutrophil reconstitution, but increased the risk of extensive chronic GVHD in patients with allo-HSCT.</p>

Role of IL-10 gene polymorphisms in promotor region in HLA matched sibling donor allogeneic hematopoietic stem cell transplantation / 中华器官移植杂志

Objective To explore the impact of IL-10 gene polymorphisms on the outcome in HLA matched sibling hematopoietic stem cell transplantation (HSCT).Methods PCR-sequencespecific primer (PCR-SSP) assay was used to analyze the SNP of IL-10 in 77 recipient and donor pairs:-1082 A/G,-819 T/C,-592 C/A.Results IL-10 ATA/ATA (1082,-819,-592) genotype in recipients significantly decreased the incidence of grade Ⅱ-Ⅳ acute graft vursus-host disease (aGVHD) (6.1％ vs.25.0 ％,P＜0.05),reduced 5-year transplant-related mortality (TRM) (10.7 ％± 5.9％ vs.29.7％ ± 5.2％,P＜0.05) and increased disease free survival (DFS) (81.8％ ± 6.7％ vs.56.8％ ± 7.5％,P＜0.05).With regard to the donor genotype,the incidence of grade Ⅱ-Ⅳ aGVHD,extensive chronic GVHD,5-year TRM and DFS had no signicant difference between IL-10 ATA/ATA and non ATA/ATA subgroup.Multivariable analysis also revealed that IL-10 non-ATA/ATA genotype in recipients and high-risk status of disease were two independent risk factors for DFS (HR =2.911,P =0.029; HR =2.686,P =0.027).Conclusion In HLA-matched sibling HSCT,the presence of recipient IL-10 ATA/ATA significantly decreased the incidence of grade Ⅱ-Ⅳ aGVHD and TRM,and increased DFS.

Hematopoietic stem cell transplantation in combination with imatinib for treatment of Philadelphia chromosome positive acute lymphoblastic leukemia / 中华器官移植杂志

Objective To analyze the outcomes and the prognostic factors of hematopoietic stem cell transplantation (HSCT) in combination with imatinib for Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL). Methods All 32 patients with Ph+ ALL achieved hematologic complete remission (CR) at time of transplantation, including 27 cases in the first CR (CR1) and 5 in CR2. Nineteen patients achieved molecular remission (MR). Among 32 patients, 4 received autologous HSCT (AHSCT), and 28 allogeneic HSCT (allo-HSCT). The conditioning regimens comprised of total body irradiation (TBI), cyclophosphamide, fludarabine and cytarabine. The median number of transfused mononuclear cells was 5. 6 × 108/kg, and that of CD34+ cells was 2. 94 × 106 /kg. Thirty-one patients were administrated imatinib orally before transplantion, at a dose of 400～600 mg/day, and 16 patients after transplantation, including 7 for prevention at a dose of 300～400 mg/day and 9 for salvage treatment at a dose of 400 ～ 600 mg/day. Results Hematopoietic reconstitution was achieved in all 32 patients. Three-year estimate of overall survival (OS) was (62. 1±8. 6)%, leukemia-free survival (LFS) (59. 2 ± 8. 7)%, relapse rate (RR) (17. 7 ± 7. 2)% and transplant-related mortality (26. 2 ± 8. 0) %. All 4 undergoing AHSCT were alive, and 3 out of them were in continuous CR with durations of 14, 18 and 67 months respectively. The univariate analysis for prognosis in allo-HSCT showed that the OS of HLA-matched sibling donors group was 76. 5 %,higher than that of unrelated or haploidentical donors group (27. 3 %, P＜0. 05), and so was LFS (70. 6 % vs 27. 3 %, P＜0. 05). RR in patients achieving MR at time of transplantation was 5. 6 %,lower than that in those not achieving MR (40. 0 %, P＜0. 05). RR in patients in CR1 at time of transplantation was 12. 5 %, lower than that in those in CR2 (50 %, P ＜0. 05). Conclusion Imatinib improved the outcomes of HSCT for Ph+ ALL, especially to patients achieving MR at time of transplantation and transplantation in early stage (CR1).

Effect of Umbilical Cord Blood Stem Cell Transplantation on Axon Regeneration in Spinal Cord-injured Rats / 天津医药

Objective: To explore the effect of umbilical cord blood stem cell transplantation on axon regeneration in spinal cord injury (SCl)in rats. Methods: The umbilical cord blood was collected and prepared into suitable concentration of CD34 positive stem cells. Thirty SD rats were divided into two groups randomly. One group served as control, another one was the treatment group. The models of spinal cord contusion injury were made by Allen's weight dropping method. One week later,the treatment group was transplanted with 10x105 umbilical cord blood stem cells with Hamilton micro-syringe at the sites of rostral and caudal to the lesioned zone respectively, while control group received just the same volume of PBS injection. Five rats in each group were sacrificed at 1 w, 2 w and 6 w after this operation. Histological and immunohistochemieal examinations including GAP-43 and NF200 were used to evaluate axon regeneration. Meanwhile, BBB motion scoring and inclined plane test were performed to assess the motion function changes of hindlimbs. Results: Compared to the control group, the area of cavity in the lesioned spinal cord region decreased significantly and the expressions of GAP-43 and NF200 increased markedly in cell transplantation group. Also the motion function had better restoration in the treatment group. Conclusion: Transplantation of umbilical cord blood stem cell may achieve both morphological and behavioral improvement for the injured spinal cord.