Objective To retrospectively analyze the engraftment, transplant-related complications and survival after unrelated cord blood transplantation (UCBT) in patients with hematologic malignancies. Methods Fifty consecutive patients with hematological malignancies (median age, 19 years; median weight, 53 kg) were treated with UCBT in single center from April 2000 to August 2009. Thirty-nine patients were high-risk or refractory. Double UCB grafts were used for 26 patients, while single UCB graft for 24 patients. Myeloablative conditioning was given to 45 cases and non-myeloablative regimens to 5 cases. All patients were given a combination of cyclosporin A (CsA) and mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis. Results The median total nucleated cell (TNC) dose was 4.0 (range, 1.95-16.24)×10~7 TNC/ kginfused, and CD34~+ cell dose was 2.74(range, 0.67-29.28)×10~5/kginfused. Forty-two of 50 patients acquired engraftment with implantation rate being 86%. The median time to engraftment (absolute neutrophil count>500/mm~3 and platelets 20 000/L) was 19 and 34 days. The cumulative incidence of neutrophil engraftment by day 42 was 86.3%(95% confidence interval [CI] 0.769-0.957); the cumulative incidence of platelets engraftment by day 120 was 72.3% (95% CI 0.620-0.821). Twenty cases developed acute GVHD, and the incidence of acute GVHD of grades Ⅲ/Ⅳ by day 100 was 7.1%. The incidence of chronic GVHD within 2 years was 17.4%. During a median follow-up period of 22 months (range 4-116), Overall 6-month, 1-year and 2-year survival rate was 66.2%(95% CI 0.590-0.734), 57.4%(95% CI 0.496-0.652), 54.2%(95% CI 0.462-0.622), respectively. For the patients with non-advanced hemotologic malignancies, 6-month, 1-year and 2-year survival rate was 73.2% (95% CI 0.659-0.805), 66.1% (95% CI 0.579-0.743), and 62.2% (95% CI 0.542-0.682) respectively. Five cases relapsed. The cumulative incidence of relapse within 2 years was 16.2% (95% CI 0.099-0.225). Twenty-one cases died mainly due to infection. Conclusion UCBT could be safely and effectively used for adult patients with hematologic malignancies.

[Objective] To retrospectively analyze the outcome of unrelated umbilical cord blood transplantation in the treatment of aggressive-phase chronic myeloid leukemia.[Methods] Fourteen consecutive patients with aggressive-phase chronic myeloid leukemia were treated with unrelated umbilical cord blood transplantation,thirteen patients were treated with myeloablative unrelated CBT and one patients were treated with nonmyeloablative unrelated CBT.All patients received standard cyclosporine A (CsA) and mycophenolate mofetil(MMF) as a graft-versus-host disease (GVHD) prophylaxis.[Results] 14 patients were all successfully engrafted.The median times for their neutrophil returning to ≥0.5×109/L and for platelet returning to ≥20×109/L were 22.8 days and 37.8 days,respectively.Acute GVHD occurred in 10 of 13 evaluable patients.The grading of acute GVHD was gradeⅡ-Ⅳin 6 patients(46.2 ％).Chronic GVHD occurred in 7 of 11 evaluable patients(63.6％).Relapse occurred in 2 of 15 patients,lextramedullary relapse was included.9 of 14 patients were alive and event-free after CBT.The probability of OS rate at 5 years was 64.3 ％,the probability of DFS rate at 5 years was 5,7.1％.[Conclusion]Unrelated umbilical cord blood transplantation is effective in the treatment of aggressive-phase chronic myeloid leukemia.

Objective To study the syndrome of inappropriate ADH secretion(SIADH)after all ogeneic hematopoietic stem cell transplantation(allo-HSCT)and the possible etiology.Methods SIADH was occurred in one patient with acute lymphoblastic leukemia who received secondary haploidentical stem cell transplantation after graft failure following umbilical cord blood transplantation.Results An 11-year-old boy was diagnosed as high-risk acute lymphoblastic leukemia,and the transplantation of unrelated double umbilical cord blood was performed for the first time,however,there was no engraftment at 28 days after the first transplantation.Secondary haploidentical stem cell transplantation was administered at day 33 after the first transplantion.The bone marrow and the peripheral blood stem cells from the patient's father transplantation was adopted.Pre-engraftment syndrome was developed in the patient at day 7 after secondary haploidentical HSCT followed by severe hyponatraemia(lowest serum sodium 115.8 mmol/L),natriuresis,hypo-osmolality of plasma,and twitch at day 26 after allo-HSCT.Then SIADH was diagnosed.The clinical condition was improved after restriction of water and administration of hypertonic saline,and eventually SIADH was controlled completely.By now,the patient had lived free of disease more than one year,with a normal diet and serum sodium in normal ranges.Conclusions SIADH after allo-HSCT is a rare fatal acute complication of central nervous system,whic h are probably associated with numerous transplant-related causes.Early accurate diagnosis and treatment promptly are great importance.

[Objective]To study the discipline of implantation and implantation dynamics in unrelated double umbilical cord blood transplantation(DUCBT).[Methods]Twenty-nine patients with hematologic malignancies who undergoing two-units unrelated donor cord blood transplantation were included in the study.After transplantation,hematopoietic chimerism of peripheral blood was evaluated by the Results of short tandem repeat with polymerase chain reactions(STR-PCR)which quantitatively determinated 16 specific alleles between donor and receptor, to find out their chimerism dynamic change, to judge whether transplantation was implanted and judge which one was implanted,and to study the discipline of implantation in DUCBT.At the same time,total nucleated cells(TNC),dose of CD34 cells,colony forming unit(CFU),colony forming unit-granulocyte and macrophage(CFU-GM),dose of CD; cells,dose of natural killer(NK)cells were compared between dominant units and non-dominant ones,to quest the discipline implantation dynamics of DUCBT.[Results]In 29 clinical cases,23 cases obtained engraftment,including 22 cases appearing one unit cord blood engraftment and 1 case appearing two units cord blood engraftment.Of 22cases with one dominant unit engraftment,at 14 days after DUCBT,the results of STR-PCR showed that 20cases appeared one dominant unit engraftment,other 2 cases appeared one dominant unit engraftment at 21days after DUCBT.Of 6 cases without engraftment,at 14 days after DUCBT,2 cases showed chimerism of two units cord blood,other 4 cases showed chimerism of two units cord blood or one unit cord mixed with receptor.At 30 days after DUCBT,their STR-PCR results of bone marrow showed full donor chimerism.Compared results at day 7,day 14,day 21 by peripheral blood,and day 30 by bone marrow with results of implantation after DUCBT,their coherence were kappa=0.112,P=0.198,kappa =0.811,P =0.001,kappa =0.900,P =0.001 and kappa =0.900,P =0.001,respectively.In addition,compared dominant unit with nondominant unit,TNC,doses of CD+34 cells,CFU,CFU-GM,CD; cells and NK cells were all no significant difference between them (P=0.783,0.455,0.615,0.534,0.114,0.463,respectively).[Conclusion]STR-PCR which quantitatively determinates 16 specific alleles between donor and receptor is sensitively and specifically to judge implant status.The 14 days after DUCBT was the time when implant is embedded.However,the implantation dynamics of DUCBT is still unknown which need further quest in the future.

Objective To study the curative efficacy and safety of single-unit umbilical cord blood transplantation (sUCBT) for malignant hematologic diseases,which is provided by China's public cord blood bank.Methods We retrospectively analyzed 409 cases of malignant hematologic diseases who accepted myeloablative single-unit unrelated donor UCBT without ATG at our center between May 2008 and December 2016.A comparative analysis was made on the total nuclear cells (TNC) of the umbilical cord blood before freezing and after thawing,the cells of CD34+,the recovery rate of cells and the clinical effect of UCBT.Result 409 units of umbilical cord blood used in UCBT respectively came from eight China's public cord blood banks.The average TNC of 409 units of umbilical cord blood before freezing and after the tubular recovery were respectively 18.5 × 108 and 16.34 × 108 (p =0.000).The average recovery rate of the tubular recovery was 88.5％,and there was significant difference among cord blood banks (P =0.000).The average TNC of umbilical cord blood before freezing and transfusion were respectively 18.5 × 108 and 15.86 × 108 (p =0.000).The average recovery rate of umbilical cord blood transfusion was 85.9％,with the difference being significant among cord blood banks (P =0.000).The average number of CD34+ cells before freezing and after the tubular recovery was 11.18 × 106and 8.68 × 106 (p =0.000).The average recovery rate of CD34+ cells after the tubular recovery was 80.75 ％,with the difference being significant among the cord blood banks (P =0.000).At 42nd day after UCBT,the cumulative incidence of neutrophil engraftment was 95.4％,and the median time of the engraftment was 17 days (11-38 days).The cumulative incidence of platelet engraftment at 120th day was 84.6％,and the median time of the engraftment was 36 days (14-93 days).The cumulative incidence of erythrocyte engraftment at 60th day was 92％,and the median time of engraftment was 22 days (9d-60 days).After the umbilical cord blood provided by each bank was used in UCBT,it got the difference in cumulative incidence of engraftment.The P values for cumulative incidence of neutrophil,platelet and erythrocyte engraftment were respectively 0.004,0.01 and 0.000 2,with the differences being statistically significant.At 100th day after UCBT,the cumulative incidence of Ⅱ-Ⅳ and Ⅲ-Ⅳ degrees of acute graft-versus-host disease (aGVHD) was respectively 28.63％ and 15.7％.After umbilical cord blood provided by each bank was used in UCBT,it got the difference in cumulative incidence of aGVHD.There was no significant difference between Ⅱ-Ⅳ and Ⅲ-Ⅳ degrees (P =0.809 and 0.68 respectively).At 3rd year after UCBT,the cumulative incidence of relapse was 15.89％.After umbilical cord blood provided by each bank was used in UCBT,there was no significant difference in the cumulative incidence of relapse (P =0.898).At 3rd year after UCBT,the overall survival (OS) rate and disease free survival (DFS) rate were respectively 66.7％ and 59％.After umbilical cord blood provided by each bank was used in UCBT,it got the difference in OS and DFS.There was no significant difference in OS and DFS (P =0.566 and 0.703 respectively).At 3rd year after sUCBT,the rate of graft-versus-host diseases/relapse-free survival (GRFS) was 54.3％.After umbilical cord blood provided by each bank was used in UCBT,there was no significant difference in the rate of GRFS (P =0.449).Conclusion The umbilical cord blood provided by China's public cord blood bank was used in UCBT.It has a high safety and good efficacy in treating malignant hematologic diseases.But it needs to set up the standardized and normalized quality-control system of umbilical cord blood for China's public cord blood bank.

Objective: To compare the efficacy of unrelated cord blood transplantation (UCBT) and HLA-identical sibling peripheral blood stem cell transplantation (PBSCT) for the treatment of adult hematological malignancies. Methods: From April 2011 to December 2015, a total of 81 patients receiving single-unit UCBT and 57 patients receiving HLA-identical sibling PBSCT were enrolled in this study. All of the patients received myelablative conditioning. Cyclosporine combined with mycophenolate mofetil was adopted for GVHD prophylaxis. Results: The cumulative incidence of neutropil engraftment at day-42 was 95.0% and 100% in UCBT and sibling PBSCT groups, respectively (P=0.863) . Platelet engraftment at day 100 was 87.3% (95%CI 76.8%-93.1%) in UCBT group, which was significantly lower than that of sibling PBSCT group[98.2% (95%CI 87.3%-99.7%) ] (P=0.005) . There were no significant differences in terms of Ⅱ-Ⅳ acute GVHD or Ⅲ-Ⅳ acute GVHD in two groups (P=0.142, 0.521) . The 3-year chronic GVHD and extensive chronic GVHD were 14.9% (95%CI 5.2%-23.5%) and 11.2% (95%CI 2.9%-18.7%) , respectively in UCBT group, which was significantly lower than that of sibling PBSCT group[35.2% (95%CI 19.4%-47.8%) , 31.4% (95%CI 16.2%-43.9%) ] (P=0.008, 0.009) . The 3-year transplant-related mortality (TRM) was similar between two groups (30.1% vs 23.2%, P=0.464) . The relapse rate at 3-year in UCBT group[12.9% (95%CI 6.6%-21.5%) ]was significantly lower than that in sibling PBSCT group[24.3% (95%CI 13.5%-36.8%) ] (P=0.039) . There were no significant differences in terms of overall survival (OS) and disease-free survival (DFS) between two groups (58.6% vs 54.8%, P=0.634; 57.0% vs 52.4%, P=0.563) . But GVHD-free and relapse-free survival (GRFS) in UCBT group [55.7% (95%CI 44.1%-65.8%) ]was significantly higher than that of sibling PBSCT group[42.9% (95%CI 29.8%-55.3%) ] (P=0.047) . Conclusions For adult hematological malignancies, the incidences of acute GVHD and TRM were similar between UCBT and sibling PBSCT recipients, and the incidences of chronic GVHD and relapse were lower in UCBT recipients. UCBT recipients had higher GRFS rate although OS and DFS were similar between two groups, which may reflect the real recovery and better quality of life following UCBT.

Objective:To retrospectively analyze the clinical outcomes of single unrelated cord blood transplantation (UCBT) in children with high risk and refractory acute myeloid leukemia (AML) .Methods:Between June 2008 and December 2018, a total of 160 consecutive pediatric patients with AML received single UCBT (excluding acute promyelocytic leukemia) . Myeloablative conditioning (MAC) regimen were applied. All patients received a combination of cyclosporine A (CsA) and mycophenolate mofetil (MMF) for the prophylaxis of graft -versus- host disease (GVHD) .Results:The cumulative incidence of neutrophil cells engraftment at day +42 and platelet recovery at day +120 was 95.0% (95% CI 90.0%-97.5%) at a median of 16 days after transplantation (range, 11-38 days) and 85.5% (95% CI 83.3%-93.4%) with a median time to recovery of 35 days (range, 13-158) , respectively. Incidence of grades Ⅱ-Ⅳ and Ⅲ-Ⅳ acute GVHD and chronic GVHD were 37.3% (95%CI 29.3%-45.2%) , 27.3% (95% CI 20.0%-35.0%) and 22.4% (95% CI 15.5%-28.7%) , respectively. The transplant-related mortality (TRM) at 360 day was 13.1% (95% CI 8.4%-18.9%) . The 5-year cumulative incidence of relapse was 13.8% (95% CI 8.5%-20.3%) . The 5-year disease-free survival (DFS) and overall survival (OS) were 71.7% (95% CI 62.7%-77.8%) and 72.2% (95% CI 64.1%-78.7%) , respectively. The 5-year GVHD and relapse free survival (GRFS) was 56.1% (95% CI 46.1%-64.9%) . The 5-year cumulative recurrence rates of CR1, CR2, and NR groups were 5.3%, 19.9%, and 30.9% ( P=0.001) , and the 5-year OS rates were 79.9% (95% CI 70.3%-86.7%) , 71.1% (95% CI 50.4%-84.4%) and 52.9% (95% CI 33.0%-69.3%) ( χ2=7.552, P=0.020) , respectively. Conclusions:For pediatric patients with high risk and refractory AML, UCBT is a safe and effective treatment option, and it is favorable to improve the survival rate in CR1 stage.

Objective:To evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection in the treatment of peripheral T-cell lymphoma (PTCL) in a real-world setting.Methods:This was a real-world ambispective cohort study (MOMENT study) (Chinese clinical trial registry number: ChiCTR2200062067). Clinical data were collected from 198 patients who received mitoxantrone hydrochloride liposome injection as monotherapy or combination therapy at 37 hospitals from January 2022 to January 2023, including 166 patients in the retrospective cohort and 32 patients in the prospective cohort; 10 patients in the treatment-na?ve group and 188 patients in the relapsed/refractory group. Clinical characteristics, efficacy and adverse events were summarized, and the overall survival (OS) and progression-free survival (PFS) were analyzed.Results:All 198 patients were treated with mitoxantrone hydrochloride liposome injection for a median of 3 cycles (range 1-7 cycles); 28 cases were treated with mitoxantrone hydrochloride liposome injection as monotherapy, and 170 cases were treated with the combination regimen. Among 188 relapsed/refractory patients, 45 cases (23.9%) were in complete remission (CR), 82 cases (43.6%) were in partial remission (PR), and 28 cases (14.9%) were in disease stabilization (SD), and 33 cases (17.6%) were in disease progression (PD), with an objective remission rate (ORR) of 67.6% (127/188). Among 10 treatment-na?ve patients, 4 cases (40.0%) were in CR, 5 cases (50.0%) were in PR, and 1 case (10.0%) was in PD, with an ORR of 90.0% (9/10). The median follow-up time was 2.9 months (95% CI 2.4-3.7 months), and the median PFS and OS of patients in relapsed/refractory and treatment-na?ve groups were not reached. In relapsed/refractory patients, the difference in ORR between patients with different number of treatment lines of mitoxantrone hydrochloride liposome injection [ORR of the second-line, the third-line and ≥the forth-line treatment was 74.4% (67/90), 73.9% (34/46) and 50.0% (26/52)] was statistically significant ( P = 0.008). Of the 198 PTCL patients, 182 cases (91.9%) experienced at least 1 time of treatment-related adverse events, and the incidence rate of ≥grade 3 adverse events was 66.7% (132/198), which was mainly characterized by hematologic adverse events. The ≥ grade 3 hematologic adverse events mainly included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and anemia; non-hematologic adverse events were mostly grade 1-2, mainly including pigmentation disorders and upper respiratory tract infection. Conclusions:The use of mitoxantrone hydrochloride liposome injection-containing regimen in the treatment of PTCL has definite efficacy and is well tolerated, and it is a new therapeutic option for PTCL patients.

Drug Resistance, Multiple, Bacterial ; Gram-Negative Bacteria ; drug effects ; Hematologic Neoplasms ; microbiology ; Humans ; Minocycline ; administration & dosage ; analogs & derivatives ; therapeutic use ; Retrospective Studies

OBJECTIVETo evaluate the therapeutic efficacy and related risk factors of acute myelogenous leukemia （AML） patients treated with unrelated cord blood transplantation （UCBT）.

METHODSA retrospective analysis was performed on the clinical data of 58 AML patients that consisted of 1 case of M0, 1 case M1, 35 cases M2, 3 cases M4, 14 cases M5, 3 cases M6, and 1 case acute mixed leukemia, respectively. Of them, 1 case AML secondary to myelodysplastic syndrome, and 36 in first complete remission （CR1）, 14 in second complele remission （CR2）, 8 in non- remission （NR）, 43 cases were refractory or high-risk patients（70.1%）. The median age was 14.5 years with the median weight of 45 kg, 49 patients received sUCBT and 9 dUCBT. All the patients conditioned with intensified myeloablative regimen and received a combination of Cyclosporine A（CsA）and mycophenolate mofetil（MMF）to prevent graft- versus- host disease（GVHD）.

RESULTS56 out of 58 patients achieved engraftment with implantation rate 96.6%. The median time of ANC≥0.5×10⁹/L was 17（12-37）days, and that of PLT≥20× 109/L 33（17-140）days respectively. 24 cases developed acute GVHD（aGVHD）, the incidence rate of grade Ⅱ to Ⅳ aGVHD was 30.4%. The chronic GVHD（cGVHD）was occured in 7 patients of the 49 evaluable patients, all were limited. The estimated 3-year overall survival（OS）and disease-free survival （DFS）were（60.3±6.4）% and（60.1±6.5）% respectively. And the cumulative incidences of 3-year nonrelapse mortality（NRM）and relapse were 33.3% and 9.1% respectively. The 3- year OS rates of AML patients were（66.0 ± 6.7）% for CR and（25.0 ± 15.3）% for NR, differences were statistical significance.

CONCLUSIONFor AML patients, UCBT was conducive to improve outcome with lower incidences of cGVHD and relapse, the patients after transplantation could obtain high quality of life.

Acute Disease ; Adolescent ; Cyclosporine ; Disease-Free Survival ; Fetal Blood ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Incidence ; Leukemia, Myeloid, Acute ; Mycophenolic Acid ; analogs & derivatives ; Quality of Life ; Recurrence ; Remission Induction ; Retrospective Studies