CYTOMEGALOVIRUS INTERSTITIAL PNEUMONITIS FOLLOWING ALLOGENEIC PERIPHERAL BLOOD STEM CELL TRANSPLANTATION

Objective： To explore the risk factors and prophylaxis and treatment of cytomegalovirus interstitial pneumonitis （CMV-IP） after allogeneic peripheral blood stem cell transplantation （allo-PBSCT）. Methods： 43 patients who received allo-PBSCT were allocated to either a Gancyclovir（GCV）-prophylaxis group （n=19） or a non-GCV prophylaxis group （n=24）. A comparison was made of the incidence of CMV-IP in patients given or not given prophylactic gancyclovir. Results： 9 patients in non-GCV prophylaxis group developed late CMV-IP （P〈0.05）. Graft-versus-host-disease （GVHD） may be associated with a high risk of CMV-IP. 5 cases of CMV-IP were successfully treated with GCV, but 3 cases died of CMV-IP. The most common adverse event of GCV was neutropenia, but was reversible. Conclusion： CMV infection was a major cause of interstitial pneumonitis after allo-PBSCT, which correlated strongly with the severity of GVHD. Gancyclovir was shown to be effective in both prophylaxis and treatment of CMV-IP.

The Safety of Autologous Peripheral Blood Stem Cell Transplantation by Intracoronory Infusion in Patients with Acute Myocardial Infarction

Objectives Bone-marrow stem-cell transplantation has been shown to improve cardiac function in patients with acute myocardial infarction (AMI) , but the safety of intracoronory infusion of autologous peripheral blood stem-cell (PBSCs) in patients with AMI is unknown. For this reason, we observe the feasibility and safety of PBSCs transplantation by intracoronory infusion in such patients. Methods 41 patients with AMI were allocated to receive granulocyte colony-stimulating factor (G- CSF: Filgrastim,300μg) with the dose of 300μg~ 600μg/day to mobilize the stem cell, and the duration of applying G-CSF was 5 days. On the sixth day, PBSCs were separated by Baxter CS 3000 blood cel 1 separator into suspend liquid 57 ml. Then the suspend liquid was infused into the infarct related artery (IRA) by occluding the over the wire balloon and infusing artery through balloon center lumen. In the process of the intracoronary infusion of PBSCs, the complications should be observed, which were arrhythmias including of bradycardia, sinus arrest or atrial ventricular block, premature ve. ntricular beats ,ven~icular tachycardia, ventricular fibrillation; and hypotention, etc. Results There were total 10 cases with complications during the intracoronary infusion of PBSCs. The incidence of complications was 24.4% (10/41), including bradyca- rdia was 2.4 % (1/41), sinus arrest or atrial ventri- cular block was 4.0% (2/41), ventricular fibrillation was 2.4 % (1/41), hypotention was 14.6 % (6/41). Conclusions In patients with AMI, intracoronary infusion of PBSCs is feasible and safe.

Autologous peripheral blood stem cell transplantation in the patients with hematologic malignancies and solid tumors

Objective To evaluate the long-term therapeutic effects of autologous peripheral blood stem cell transplantation (auto-PBSCT) on the treatment of hematological and solid tumors.Methods Fifty-one patients were recruited in this auto-PBSCT study, in which several potentially important parameters were studied including the optimal time for stem cell collection, the dose of stem cell reinfusion, the time of hematopoietic reconstitution, the disease free survival (DFS) and overall survival (OS), complications related to transplantation, and maintenance chemotherapy after auto-PBSCT.Results After APBSCT, 3-year and 5-year survival rates of NHL were 83.3%; those of AML were 74.7%; those of MM were 37.9% and 19%; those of ALL were 40% and 0% respectively. Hematopoietic reconstitution was greatly promoted by granulocyte colony stimulating factor (G-CSF). The mean time for patients' neutrophil to recover up to >0.5×109/L after APBSCT was 11.14 days in the group of the patients receiving G-CSF in contrast to 17.6 days in the group receiving no G-CSF. The most common complications of transplantation were fever, liver dysfunction and hypokalaemia, which were curable. No death was due to transplantation related complications.Conclusion Comparing with conventional chemotherapy, our study suggests that auto-PBSCT is a very important therapeutic option that can significantly improve the prognosis in the patients with hematological and solid tumors, especially in the patients with AML and NHL.

Efficacy and Safety of Unmanipulated Haploidentical Related Donor AIIogeneic Peripheral Blood Stem Cell Transplantation in Patients with Relapsed/Refractory Acute Myeloid Leukemia

Background： Studies of haploidentical-related donor （HRD） stem cell transplantation using a combination of peripheral blood stem cells （PBSCs） and bone marrow as the graft have reported encouraging results for patients with hematological diseases. However, few studies specifically reported transplantation of only PBSCs from HRDs among patients with relapsed or refractory acute myeloid leukemia （AML）. Here, the long-term outcomes and side effects of unmanipulated HRD PBSC transplantation （HRD-PBSCT） for relapsed/refractory AML were analyzed. Methods： We performed a retrospective analysis of the outcomes in relapsed/refractory AML patients who underwent PBSCT from HRDs （n = 36）. Results： Thirty-one （86.1%） patients in the HRD-PBSCT group achieved platelet recovery. The cumulative incidence of acute graft-versus-host disease （aGVHD） in the HRD-PBSCT group was 40.00%, and the cumulative incidence of grades 2-4 aGVHD in this group was 13.33%. A total of 13 patients in the HRD-PBSCT group had recurrent disease at a median of 183 days after transplantation （range： 10-1700 days）, reaching cumulative incidences of relapse of 50.28% at 5 years. On multivariate analysis, donor age and patient age 〉40 years were independent risk factors for inferior disease-free survival or overall survival （P 〈 0.05）. The results of the present study demonstrate rapid and complete neutrophil engraftment, a low incidence of grade 2-4 aGVHD, and promising survival rates in patients after HRD-PBSCT. Thus, granulocyte colony-stimulating factor-primed PBSCs may be a reliable graft source in unmanipulated HRD-HSCT under myeloablative conditioning when no matched sibling donor is available. Conclusions： Our results support the feasibility, effectiveness, and tolerability of PBSCs as a graft source in unmanipulated HRD transplantation under myeloablative conditioning in patients with leukemia.

Allogeneic Peripheral Blood Hematopoietic Stem Cell Transplantation for Patients with Hematologic Malignancies

To investigate the therapeutic effects and associated complications of allogeneic peripheral blood stem cell transplantation （allo-PBSCT）, 40 patients with various malignant hematopoietic diseases received allo-PBSCT. The preparative regimens were based on BUCY2 or modified BUCY2, The acute graft-versus host disease （aGVHD） was prevented by cyclosporin A and shortterm MTX regimen in all patients. Two patients from donors with one fully mismatched HLA on DRB1 locus and 4 from unrelated donor also administered Zenapox （CD25 MAb） at dosage of 1 rag/ kg every day on the day before transplantation and day 4 after transplantation. These 6 patients were also treated with mycophenolate mofetil （MMF）. Transfusion of the donor cells： The median of the transfused nucleated cells was 5.38×10^8/kg and that of the CD34^＋ cells was 7.8×10^6/kg respectively. All the patients gained hematopoietic reconstruction except one who died of infection before engraftment. Seven patients got Ⅱ°-Ⅳ° aGVHD and the incidence was 17.5 %. Fourteen patients got cGVHD and the incidence was 53.8 % in the patients who survived over 6 months. Twenty-eight patients had fever or other characteristics of infection. The median follow-up time was 13.8 months. The incidence of transplantation related mortality （TRM） was 17.5 %and 2 patients relapsed （5.0 %）. It was concluded that allo-PBSCT can reconstruct hematopoiesis quickly and is a favorable therapeutic method for leukemia.

Allogeneic peripheral blood stem cell transplantation for leukemia

Objective To observe engraftment kinetics, the incidence and severity of graft-versus-host disease (GVHD), and clinical outcome on 40 recipients undergoing allogeneic peripheral blood stem cell transplantation (allo-PBSCT).Methods From June 1997 to May 1999, forty leukemia patients with a median age of 35 years underwent allo-PBSCT. PBSC were mobilized with G-CSF at a dose of 5 μg/kg s.c. every 12 hours for 5 days. A median of 7.7 (2.0 - 16.8) × 106 CD34+ cells/kg was infused into the recipients. Busulfancyclophosphamide (BU-CY) was used as the conditioning regimen. All patients received cyclosporine A and either methotrexate ( n = 34) or methylprednisolone ( n = 6) for GVHD prophylaxis.Results Engraftment of neutrophils and platelets was achieved at a median of 13 days (9- 28 days) and 12 days (7- 60 days) respectively. Patients receiving ≥4×106 CD34+ cells/kg or given G-CSF post transplant had significantly accelerated neutrophil and platelet engraftment. Acute GVHD occurred in 17 of 40 patients (42.5％), with grade Ⅱ-Ⅳ acute GVHD in 10 patients (25％). Chronic GVHD developed in 21 (9 extensive, 12 limited) out of 30 evaluable patients (21/30, 70％) with a median follow up of 380 days (180-900 days). Transplant related mortality was 17.5％ end the relapse rate was 10％. The probability of leukemia free survival at 3 years was 72.5％.Conclusion Allo-PBSCT can provide rapid hematopoietic reconstitution without an increased incidence of acute GVHD, but may be associated with a high risk of chronic GVHD.

TSR:A User-friendly R Shiny Application for Assessment of Optimal Blood Product Selection in ABO-incompatible Hematopoietic Stem Cell Transplantation

Objective:Patients undergoing hematopoietic stem cell transplant(HSCT)need frequent transfusions,until their red blood cells(RBCs)and platelets start to recover.The safe transfusion for patients who receive ABO-incompatible HSCT is essential to the transplant process.To date,there is no user-friendly tool to choose the right blood product for transfusion treatment,despite the number of guidelines and expert advice on the subject.Methods:R/shiny is a powerful programming language for clinical data analysis and visualization.It can create interactive web applications that work in real-time.The web application named TSR was built using R programming,simplifying blood transfusion practice for ABO-incompatible HSCT witha one-click solution.Results:The TSR is divided into four main tabs.The home tab provides an overview of the application,while RBC,plasma and platelet transfusion tabs offer tailored suggestions for blood product selection in each category.Unlike traditional methods that rely on treatment guidelines and specialist consensus,TSR leverages the power of the R/Shiny interface to extract critical content based on user-specified parameters,providing an innovative approach to improve transfusion support.Conclusion:The present study highlights that the TSR enables real-time analysis,and promotes transfusion practice byoffering a unique and efficient one-key output for blood product selection to ABO-incompatible HSCT.TSR has the potential to become a widely-utilized tool for transfusion services,providing a reliable and user-friendly solution that enhances transfusion safety in clinical practice.

Isolated extramedullary ocular relapse of acute lymphoblastic leukemia after peripheral blood stem cell transplantation

Isolated extramedullary ocular relapse of acute lymphoblastic leukemia （ALL） after allogeneic peripheral blood-stem cell transplantation （allo-P-BSCT） without concomitant involvement of the bone marrow is very rare,while the common sites of extramedullary relapse are the central nervous system, skin, bone, and breasts.^1 This is the report of isolated ocular relapse without any extra- ocular involvement of ALL after allo-PBSCT confirmed by histopathology.

Outcomes of peripheral blood stem cell transplantation in patients from human leukocyte antigen matched or mismatched unrelated donors

Background AIIogeneic peripheral blood stem cell transplantation from unrelated donors （UR-PBSCT） is an alternative treatment for many hematologic diseases due to lack of human leukocyte antigen （HLA）-identical sibling donors. This study aimed to evaluate the impact of the degree of the HLA match on the clinical efficacy of UR-PBSCT. Methods Patients who underwent UR-PBSCT from September 2003 to September 2012 were retrospectively investigated. They were divided into three groups according to high-resolution molecular typing. SPSS version 17.0 was used to analysis and compare the statistics of engraftment, incidence of GVHD, other complications and survival among the groups. Results One hundred and eleven patients received UR-PBSCT, 60 of them with an HLA matched donor （10/10）, 36 of them with a one locus mismatched donor （9/10）, and 15 of them with a two loci mismatched donor （8/10）. Similar basic characteristics were found in the three groups. No differences were found in engraftment of myeloid cells or platelets in the three groups （P〉0.05）. Two-year cumulative incidence of relapse, overall survival （OS） and disease-free survival （DFS） among those three groups were similar （P〉0.05）. The cumulative incidence of 100-day Ill-IV aGVHD in the HLA matched group and the one HLA locus mismatched group were significantly lower than that in the two HLA loci mismatched group （3.3%, 8.6%, and 26.7%, P=0.009）. The occurrence rate of new pulmonary infections in the HLA matched group was lower than in the two HLA mismatched groups （26.67%, 52.78%, and 41.18%, P=0.035）. The cumulative incidence of 100-day and 2-year transplantation related mortality （TRM） in two HLA loci mismatched group was higher than in the HLA matched group and in the one HLA locus mismatched group, （8.4%, 11.8% and 33.3%, P=0.016） and （12.3%, 18.7% and 47.5%, P=0.002）. Conclusions HLA mismatch will not significantly impact the engraftment or 2-year survival after UR-PBSCT, but two mismatched HLA loci may increase the cumulative incidence of severe aGVHD and TRM. Chin Med J 2014;127 （14）： 2612-2617

Transplantation of mobilized peripheral blood mononuclear cells for peripheral arterial occlusive disease of the lower extremity

Objectives To assess the clinical efficacy,safety,and feasibility of autologous transplantation of mobilized peripheral blood mononuclear cells(PBMNCs)for patients with peripheral arterial occlusive disease(PAOD)of the lower extremity.Methods A total of 152 patients with PAOD of the lower extremity were enrolled into this non-controlled observational study from November 2003 to March 2006.All patients received subcutaneous injections of recombinant human granulocyte colony-stimulating factor(G-CSF,450-600μg/day)for 5 days in order to mobilize stem/progenitor cells;their PBMNCs were collected and transplanted by multiple intramuscular injections into ischemic limbs.Patients were followed up for at least 12 weeks.Results At 12 weeks,primary manifestations,including lower limb pain and coldness,were significantly improved in 137(90.1%)of the patients;limb ulcers improved or healed in 46(86.8%)of the 53 patients,while 25 of the 48(47.9%)patients with limb gangrene remained steady or improved.Ankle-brachial index(ABI)improved in 33(22%)of the cases,and TcPO_(2) increased in 45(30%)of the cases.Angiography before treatment,and at 12 weeks after treatment,was performed in 10 of the patients and showed formation of new collateral vessels.No severe adverse effects or complications specifically related to cell transplantation were observed.Conclusion Autologous transplantation of G-CSF-mobilized PBMNCs might be a safe and effective treatment for lower limb ischemic disorder.

Skin Disinfection with 2% Chlorine Gluconate-Adine in Autologous Peripheral Hematopoietic Stem Cell Transplantation Patients

Background: Autologous peripheral blood hematopoietic stem cell transplantation is widely used in the treatment of malignant lymphoma. Patients are prone to infection during the transplantation immune deficiency period. There has been a lot of clinical research into how to better manage this period of vulnerability. Objective: This study aims to investigate the efficacy of 2% chlorhexidine gluconate (CHG) for skin disinfection in patients undergoing autologous hematopoietic stem cell transplantation (HSCT) and observe any adverse reactions. Methods: A total of 106 patients receiving autologous hematopoietic stem cell transplantation from November 2019 to December 2020 in our district were selected as the control group. From January 2021 to January 2022, 106 patients with autologous hematopoietic stem cells were included in the experimental group. The control group used the immersion bath method. The experimental group was treated with an improved scrub bath method (including 3M 2% chlorhexidine gluconate medical sanitary wipes to wipe the whole skin once). Results: The bacteria-carrying rate of the improved method (37.74%) was significantly better than that of the traditional soaking method (72.64%), and the difference was statistically significant (P Conclusion: The improved bath/wipe method has a significant positive effect on skin disinfection for patients undergoing HSCT.

Allogeneic hematopoietic stem cell transplantation in a 3-year-old boy with congenital pyruvate kinase deficiency: A case report

BACKGROUND The understanding regarding genetic variation,pathophysiology,and complications associated with pyruvate kinase deficiency(PKD)in red blood cells has been explained largely,and supportive treatment is currently the main management strategy.Etiotropic managements,including transplantation and genome editing,supplying for substitute dugs of the pyruvate kinase,are all under research.CASE SUMMARY We herein report a 3-year-old boy with severe transfusion-dependent PKD cured by unrelated identical peripheral blood stem cell transplantation(PBSCT).Hemoglobin was corrected to a normal level by gene correction after PBSCT,with no complication related to the transplantation.CONCLUSION Hematopoietic stem cell transplantation could be a substitute for transfusiondependent PKD.

Impact of Human Leukocyte Antigen Loci and Haplotypes on Intestinal Acute Graft-versus-host Disease after Human Leukocyte Antigen-matched Sibling Peripheral Blood Stem Cell Transplantation

Background： Acute graft-versus-host disease （aGVHD） is a common and severe complication of allogeneic hematopoietic stem cell transplantation （allo-HSCT）. Some studies have found that the presence of certain specific human leukocyte antigen （HLA） loci could affect the occurrence of aGVHD. Meanwhile, the impact of HLA haplotypes on aGVHD has been rarely studied. This study aimed to investigate the effects of HLA loci and haplotypes on intestinal aGVHD. Methods： Totally, 345 consecutive patients undergoing first HLA-matched sibling peripheral blood stem cell transplantation （PBSCT） from February 2004 to June 2013 at Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, were enrolled in this study. HLA loci and haplotypes of recipients with frequency over 5% were searched and their effects on intestinal aGVHD were investigated. Other important factors including donor age, recipient age, donor-recipient sex combinations, and conditioning regimens were also evaluated using logistic regression. Pure upper gastrointestinal tract aGVHD without diarrhea was excluded because the histological proof was unavailable. The follow-up end-point was 6 months after HSCT. Results： The cumulative incidence of intestinal aGVH D was 19.4%, with 18.0% of the patients classified as classic aGVH D and 1.4% as persistent, recurrent, or late aGVH D. Multivariate analysis showed that HLA-A31 locus （odds ratio [OR] 2.893, 95% confidence interval [CI] [1.054, 7.935], P = 0.039）, H LA B40-DR 15 （OR 3.133, 95% CI [1.250, 7.857], P = 0.015）, and HLA B46-DR9 haplotypes （OR 2,580, 95% CI l1.070, 6.220], P- 0.035）, fizmale donor for male recipient （OR 2.434, 95% （27 [1.319, 4.493], P = 0.004） were risk factors tbr intestinal aGVHD. Conclusion： The presence of certain HLA loci and haplotypes may influence the occurrence of intestinal aGVHD in PBSCT with HLA-identical sibling donors.

STUDIES ON THE PROPERTY AND TRANSPLANTATION OF HAEMOPOIETIC STEM CELLS FROM PERIPHERAL BLOOD

Comparative studies of the properties of murine haemopoietic stem cells from differentsources revealed that the peripheral haemopoietic stem cell is relatively weaker than the haemo-poietic stem cell from bone marrow in promoting the recovery of hemopoiesis in the irradiatedanimals. This is due to the heterogenity of stem cell population in which some aged cellsub-populations aro co-existing. The modified potential in proliferation and differentiation ofhaemopoietic stem cells in the peripheral blood seems to be irreversible under normal physio-logical conditons.In a preliminary experiment, the use of an anti-thymocyte immunoglob-ulin to eliminate immunocompetent cells proved effective in reducing the severity and incidenceof secondary diseases and in increasing the number of survivors of lethally irradiated semi-isologous mice after transplantation of parental peripheral mononuclear cells.