Effect of obesity on the efficacy of allogeneic hematopoietic stem cell transplantation / 白血病·淋巴瘤

Objective:To investigate the effect of obesity on the efficacy of allogeneic hematopoietic stem cell transplantation.Methods:The clinical data of 81 patients who underwent allogeneic hematopoietic stem cell transplantation from August 2017 to September 2020 in the First Affiliated Hospital of Nanjing Medical University were retrospectively analyzed. According to the body mass index (BMI), the patients were divided into the obese group (BMI≥28 kg/m 2, 11 cases) and the non-obese group (BMI<28 kg/m 2, 70 cases). The clinicopathological characteristics, hematopoietic stem cell implantation, post-transplantation complications, survival and recurrence were compared between the two groups. Univariate and multivariate survival analyses were performed by using Cox proportional hazards regression model. Results:The median follow-up time of 81 patients was 280 d (8-1 218 d). The 1-year overall survival (OS) rate was 77.9%, and the 1-year progression-free survival (PFS) rate was 73.8%. The 1-year OS rates of the non-obese group and the obese group were 82.6% and 46.2% ( χ2 = 15.54, P<0.01), and the 1-year PFS rates were 82.1% and 36.4% ( χ2 = 15.56, P<0.01). The non-recurrence mortality (NRM) rates of the non-obese group and the obese group were 7.1% and 32.7% ( χ2 = 6.463, P = 0.01), and the cumulative recurrence rate was 11.5% and 42.9% ( χ2 = 8.146, P = 0.004). Between the non-obese group and the obese group, the median engraft time of neutrophils and platelets, acute graft-versus-host disease, chronic graft-versus-host disease, hemorrhagic cystitis, cytomegalovirus infection and Epstein-Barr virus infection had no statistical difference ( P > 0.05). The result of multivariate analysis showed that obesity was an independent adverse influencing factor for OS of patients with allogeneic hematopoietic stem cell transplantation ( HR = 3.814, 95% CI 1.343-10.827, P = 0.012). Conclusion:Obesity is an important unfavorable factor that affects patient's survival after allogeneic hematopoietic stem cell transplantation, and the improvement of the efficacy and survival of these patients is worthy of further study.

Efficacy observation of standard-dose IA regimen in treatment of ≥ 55 years old newly diagnosed patients with acute myeloid leukemia / 白血病·淋巴瘤

Objective To explore the clinical efficacy and toxicity of standard-dose IA regimen as induction chemotherapy in treating initially diagnosed acute myeloid leukemia (AML) patients ≥55 years old. Methods A total of 32 patients were enrolled in this study. The remission, survival time and adverse effects after IA regimen were retrospectively analyzed. Results The complete remission (CR) rate, partial remission (PR) rate and overall response (OR) rate were 71.9%(23/32), 9.4%(3/32), 81.3%(26/32) after IA regimen. In favorable, intermediate and poor prognosis groups (grouped by cytogenetic or molecular factors), 6, 14 and 3 cases achieved CR (χ2= 5.571, P= 0.067), 1, 2 and 0 cases achieved PR, while OR rates were 100.0 %(7/7), 84.2 % (16/19), 50.0 % (3/6) (χ2= 2.114, P= 0.359). The median overall survival (OS) time of three groups were 28.07 months (6.57-46.33 months), 16.93 months (0.40-87.57 months) and 3.03 months (2.00-6.00 months) (Z=9.630, P=0.008) and the 2-year OS rates were 83.33%, 46.80%and 0, respectively (χ2=12.206, P< 0.001). Myelosuppression and infections due to neutropenia were the main adverse effects and severe non-hemotologic toxicities were not observed. Conclusion The standard-dose IA regimen can increase CR/OR rate and prolong the median OS time of patients with favorable and intermediate prognosis and it can be used as the first induction chemotherapy regimen for elderly AML patients of ≥55 years old.

Reduced intensity conditioning allogeneic hematopoietic stem cell transplantation in chronic lymphocytic leukemia (CLL) patients with the aberration of p53 gene / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the effectiveness and safety of reduced intensity conditioning allogeneic hematopoietic stem cell transplantation (RIC allo-HSCT) in ultra high risk chronic lymphocytic leukemia (CLL) patients with the deletion of p53 to deepen the understanding of allo-HSCT in the treatment of CLL.</p><p><b>METHODS</b>In this retrospective study, a total of 4 ultra high risk CLL patients with the deletion of p53 in our center between July 2012 and Jan 2014 were enrolled. The RIC regimen was administered and the hematopoietic reconstitution, transplantation related mortality (TRM), overall survival (OS), progress free survival (PFS) were evaluated.</p><p><b>RESULTS</b>We registered 4 patients with the median age of 56 years (49-61 years), including 3 males and 1 female. The median mononuclear cells (MNC) and CD34(+) cells were 6.54 (2.85-14.7) × 10(8)/kg (recipient body weight) and 5.81 (2.85-7.79) × 10(6)/kg (recipient body weight), respectively. The median time of the neutrophil recovery was 11 days (range of 9-12 days), and the median time of the platelet recovery 5.5 days (range of 0-11 days). Three patients (75%) attained a full donor chimerism at day 28 after transplantation and one (25%) got a mixed chimerism of donor and recipient. During the follow-up at a median time of 26.5 months (range of 21-39 months), 2 (50%) patients developed acute graft versus host disease (aGVHD) grade I and 2 (50%) patients got CMV infection. One patient got herpes zoster virus and EB virus infections. No transplantation related mortality was found in the 4 patients. One patient who was in partial response status progressed 5 months after transplantation, and the other 3 patients remained in durable remission after allo-HSCT.</p><p><b>CONCLUSION</b>These results suggested that RIC allo-HSCT showed durable remission, good tolerance and acceptable toxicity, which could be a better option for the treatment of ultra high risk CLL patients with the deletion of p53 and was worth to be investigated and applied widely in future.</p>

Clinical analysis of 81 cases of malignant lymphoma treated with autologous hematopoietic stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigated the curative effect of autologous hematopoietic stem cell transplantation (ASCT) for malignant lymphoma.</p><p><b>METHODS</b>The clinical data of 81 patients with malignant lymphoma received ASCT from April 1999 to October 2013 were retrospectively analyzed. Of 81 patients, 70 were non-Hodgkin's lymphoma (NHL) and 11 Hodgkin's lymphoma (HL). High dose of etoposide combined with G-CSF was used to mobilize peripheral hematopoietic stem cell. Preconditioning regimen was BEAM (carmustine + cytarabine + etoposide + melphalan).</p><p><b>RESULTS</b>Enough peripheral blood stem cells were collected from all patients. All of the patients after transplantation achieved hematopoietic reconstitution, the median time of the absolute neutrophil count (ANC) recovery to >0.5×10⁹/L time was 10(7-16) d, and the median time of platelet count recovery to >20×10⁹/L was 10(6-17) d. With the follow-up of 23(2-139) months, progression free survival (PFS) was 72.7%, and overall survival (OS) was 88.6%. The median PFS and OS were not reached. Complete remission (CR) before ASCT was an independent prognostic factor of PFS. No transplant related death happened.</p><p><b>CONCLUSION</b>ASCT was a safe and effective method for treatment of malignant lymphoma.</p>

Inhibitory effect of all-trans-retinoid and polyphenon-100 on microsatellite instability in a colon cancer line / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the effects of all-trans-retinoic acid(ATRA) and polyphenon-100 (PP) on genetic instability of human tumor cells via their role in alteration of microsatellite sequence(MS) and the expression of mismatch repair gene hMLH(1) and hMSH(2) in RER(+) (replication error) cells.</p><p><b>METHODS</b>RER(+) colon cancer cell line was used as a host for lipofection with pCMV-CAR in which a foreign (CA)(14) repeat was inserted in the coding sequence of LacZ reporter gene, resulting in misreading LacZ frame. Any mutation which made the base number of (CA)(14) tract to be 3-fold resumed normal reading frame of LacZ, and thus led to expression of beta-galactosidase. Variable expression of LacZ in the transfectant cells resulting from RATA or PP treatment was measured by OD reading at lambda 620 after X-gal staining. Expression of mismatch repair genes of hMLH(1) and hMSH(2) was examined at mRNA level by reverse transcription-polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>ATRA at 1 mu mol/L, 0.1 u mol/L and PP at 3 mu g/ml had no significant inhibitory effect on cell proliferation. After being treated with ATRA or PP for 1 week, the blue cells of RKO transfectant clones were significantly reduced, and this meant the mutation of exogenous (CA)(14) in RKO cells were inhibited. But no expression of hMLH(1) and hMSH(2) was observed.</p><p><b>CONCLUSION</b>The above data showed both ATRA and PP had inhibitory effects on MS instability of cancer and thus demonstrated directly their beneficial role in stabilization of genomic DNA. However, the present authors have not observed any expression of hMLH(1) and hMSH(2) in RKO cells treated with ATRA or PP.</p>