COVID-19 impact in Crohn’s disease patients submitted to autologous hematopoietic stem cell transplantation

BACKGROUND Severe acute respiratory syndrome coronavirus 2 is the virus responsible for coronavirus disease 2019(COVID-19),a disease that has been blamed for inducing or exacerbating symptoms in patients with autoimmune diseases.Crohn's disease(CD)is an inflammatory bowel disease that affects genetically susceptible patients who develop an abnormal mucosal immune response to the intestinal microbiota.Patients who underwent hematopoietic stem cell transplantation(HSCT)are considered at risk for COVID-19.AIM To describe for the first time the impact of COVID-19 in CD patients who had undergone autologous,non-myeloablative HSCT.METHODS In this descriptive study a series of 19 patients were diagnosed with positive COVID-19.For two patients there were reports of the occurrence of two infectious episodes.Parameters related to HSCT,such as time elapsed since the procedure,vaccination status,CD status before and after infection,and clinical manifestations resulting from COVID-19,were evaluated.RESULTS Among the patients with COVID-19,three,who underwent Auto HSCT less than six months ago,relapsed and one,in addition to the CD symptoms,started to present thyroid impairment with positive anti-TPO.Only one of the patients required hospitalization for five days to treat COVID-19 and remained in CD clinical remission.Nine patients reported late symptoms that may be related to COVID-19.There were no deaths,and a statistical evaluation of the series of COVID-19 patients compared to those who did not present any infectious episode did not identify significant differences regarding the analyzed parameters.CONCLUSION Despite the change in CD status in three patients and the presence of nine patients with late symptoms,we can conclude that there was no significant adverse impact concerning COVID-19 in the evaluated patients who underwent HSCT to treat CD.

Day 100 Absolute Monocyte/Lymphocyte Prognostic Score and Survival Post Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation in Diffuse Large B-Cell Lymphoma

Day 100 prognostic factors post-autologous peripheral blood hematopoietic stem cell transplantation (APBHSCT) to predict clinical outcomes in diffuse large B-cell lymphoma (DLBCL) patients have not been studied. Thus, we retrospectively examined if day 100 absolute monocyte/lymphocyte prognostic score (AMLPS-100) affects clinical outcomes by landmark analysis from day 100 post-APBHSCT in DLBCL. Only DLBCL patients in complete remission at day 100 post-APBHSCT were evaluated. From 2000 to 2007, 134 consecutive DLBCL patients are qualified for the study. Patients with a day 100 absolute monocyte count (AMC-100) ≥ 630 cells/μL and day 100 absolute lymphocyte count (ALC-100) ≤ 1000 cells/μL experienced inferior overall survival (OS) and progression free survival (PFS). On multivariate analysis, the AMC-100 and ALC-100 remained independent predictors of OS and PFS. Combining both values into the AMLPS-100, the 5-year OS rates for low, intermediate, and high AMLPS-100 risk groups were 94% (95% CI, 83.0% - 98.1%), 70% (95% CI, 58.6% - 80.1%), and 13% (95% CI, 3.4% - 40.5%), respectively;and the 5-year PFS rates were 87% (95% CI, 74.0% - 94.1%), 68% (95% CI, 56.0% - 77.8%), and 13% (95% CI, 3.4% - 40.5%), respectively. The AMLPS-100 is a simple biomarker score that can stratify clinical outcomes from day 100 post-APBHSCT in DLBCL patients.

Hemophagocytic lymphohistiocytosis after autologous stem cell transplantation in angioimmunoblastic T-cell lymphoma:A case report

BACKGROUND Angioimmunoblastic T-cell lymphoma(AITL), a unique subtype of peripheral Tcell lymphoma, has relatively poor outcomes. High-dose chemotherapy with autologous stem cell transplantation(ASCT) can achieve complete remission and improve outcomes. Unfortunately, subsequent T-cell lymphoma-triggered hemophagocytic lymphohistiocytosis(HLH) has a worse prognosis than B-cell lymphoma-triggered HLH.CASE SUMMARY We here report a 50-year-old woman with AITL who achieved a favorable outcome after developing HLH 2 mo after receiving high-dose chemotherapy/ASCT. The patient was initially admitted to our hospital because of multiple enlarged lymph nodes. The final pathologic diagnosis, made on biopsy of a left axillary lymph node was AITL(Stage Ⅳ, Group A). Four cycles of the following chemotherapy regimen were administered: Cyclophosphamide 1.3 g, doxorubicin 86 mg, and vincristine 2 mg on day 1;prednisone 100 mg on days 1-5;and lenalidomide 25 mg on days 1-14. The interval between each cycle was 21 d. The patient received a conditioning regimen(busulfan, cyclophosphamide, and etoposide) followed by peripheral blood stem cell infusion. Unfortunately, she developed sustained fever and a low platelet count 17 d after ACST, leading to a diagnosis of HLH after ASCT. During treatment, she experienced thrombocytopenia and Pneumocystis carinii pneumonia. The patient was successfully treated with etoposide and glucocorticoids.CONCLUSION It is possible that development of HLH is related to immune reconstitution after ASCT.

The safety of autologous peripheral blood stem cell transplantation by intracoronory infusionin in patients with acute myocardial infarction

Objective Bone-marrow stem-cell transplantation has been shown to improve cardiac function in patients with 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.Method Fourty one patients with AMI were allocated to receive Granulocyte Colony-Stimulating Factor (G-CSF:Filgrastim,300 μg) with the dose of 300 μg-600 μg/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 cell 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 ventricular beats ,ventricular 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 bradycardia is 2.4 %(1/41), sinus arrest or atrial ventricular block is 4.9%(2/41), ventricular fibrillation is 2.4 %( 1/41), hypotention is14.6 % (6 /41).Conclusions In patients with AMI, intracoronary infusion of PBSCs is feasible and safe.

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.

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.

Transplantation of autologous peripheral blood mononuclear cells in the subarachnoid space for amyotrophic lateral sclerosis:a safety analysis of 14 patients

There is a small amount of clinical data regarding the safety and feasibility of autologous peripheral blood mononuclear cell transplantation into the subarachnoid space for the treatment of amyotrophic lateral sclerosis.The objectives of this retrospective study were to assess the safety and efficacy of peripheral blood mononuclear cell transplantation in 14 amyotrophic lateral sclerosis patients to provide more objective data for future clinical trials.After stem cell mobilization and collection,autologous peripheral blood mononuclear cells（1 × 109） were isolated and directly transplanted into the subarachnoid space of amyotrophic lateral sclerosis patients.The primary outcome measure was incidence of adverse events.Secondary outcome measures were electromyography 1 week before operation and 4 weeks after operation,Functional Independence Measurement,Berg Balance Scale,and Dysarthria Assessment Scale 1 week preoperatively and 1,2,4 and 12 weeks postoperatively.There was no immediate or delayed transplant-related cytotoxicity.The number of leukocytes,serum alanine aminotransferase and creatinine levels,and body temperature were within the normal ranges.Radiographic evaluation showed no serious transplant-related adverse events.Muscle strength grade,results of Functional Independence Measurement,Berg Balance Scale,and Dysarthria Assessment Scale were not significantly different before and after treatment.These findings suggest that peripheral blood mononuclear cell transplantation into the subarachnoid space for the treatment of amyotrophic lateral sclerosis is safe,but its therapeutic effect is not remarkable.Thus,a large-sample investigation is needed to assess its efficacy further.

Autologous hematopoietic stem cell transplantation in chemotherapy-sensitive lymphoblastic lymphoma: treatment outcome and prognostic factor analysis

Objective： The study evaluated the effectiveness of autologous hematopoietic stem cell transplantation （AHSCT） in the treatment of lymphoblastic lymphoma （LL）. Methods： We relxospectively analyzed the data from 41 patients with chemotherapy-sensitive LL who underwent hematopoietic stem cell transplantation （HSCT） from December 1989 to December 2009 in a single institution. Results： HSCT was conducted as first-line consolidation therapy and salvage therapy in 36 and 5 patients, respectively. The median follow-up was 97.1 months （range, 24.6-173.1 months）. The 5-year overall survival （OS） and event-free survival （EFS） rate were 64% and 47% for the initially treated patients, respectively, and were both 20% for the relapsed ones. Bone marrow （BM） involvement and chemotherapy cycles prior to transplantation were identified as significant prognostic factors for EFS in multivariate analysis. Conclusions These results confirm that AHSCT is a reasonable option for chemotherapy-sensitive LL patients in first complete remission （CR1）.

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.

Hepatitis B-related events in autologous hematopoietic stem cell transplantation recipients

AIM: To investigate the frequency of occult hepatitis B, the clinical course of hepatitis B virus (HBV) reactivation and reverse seroconversion and associated risk factors in autologous hematopoietic stem cell transplantation (HSCT) recipients. METHODS: This study was conducted in 90 patients undergoing autologous HSCT. Occult HBV infection was investigated by HBV-DNA analysis prior to transplantation, while HBV serology and liver function tests were screened prior to and serially after transplantation. HBV-related events including reverse seroconversion and reactivation were recorded in all patients. RESULTS: None of the patients had occult HBV prior to transplantation. Six (6.7%) patients were positivefor HBV surface antigen (HBsAg) prior to transplantation and received lamivudine prophylaxis; they did not develop HBV reactivation after transplantation. Clinical HBV infection emerged in three patients after transplantation who had negative HBV-DNA prior to HSCT. Two of these three patients had HBV reactivation while one patient developed acute hepatitis B. Three patients had anti-HBc as the sole hepatitis B-related antibody prior to transplantation, two of whom developed hepatitis B reactivation while none of the patients with antibody to HBV surface antigen (anti-HBs) did so. The 14 anti-HBs-and/or anti-HBc-positive patients among the 90 HSCT recipients experienced either persistent (8 patients) or transient (6 patients) disappearance of anti-HBs and/or anti-HBc. HBsAg seroconversion and clinical hepatitis did not develop in these patients. Female gender and multiple myeloma emerged as risk factors for loss of antibody in regression analysis (P < 0.05). CONCLUSION: Anti-HBc as the sole HBV marker seems to be a risk factor for reactivation after autologous HSCT. Lamivudine prophylaxis in HbsAg-positive patients continues to be effective.

Prognostic value of ^(18)F-fluorodeoxyglucose positron emission tomography using Deauville criteria in diffuse large B cell lymphoma treated with autologous hematopoietic stem cell transplantation

Objective: High-dose chemotherapy(HDC) followed by autologous hematopoietic stem cell transplantation(auto-HSCT) plays an important role in improving outcomes of diffuse large B cell lymphoma(DLBCL) patients.18 F-fluorodeoxyglucose(18 F-FDG) positron emission tomography(PET)/computed tomography(CT) has been widely accepted in response assessment and prediction of prognosis in DLBCL. Here, we report the value of 18 FFDG PET/CT pre-and post-HSCT in predicting outcomes of patients with DLBCL.Methods: DLBCL patients who had PET/CT scan before and after HSCT were included. PET results were interpreted based upon Deauville criteria. The prognostic value of 18 F-FDG PET/CT in auto-HSCT was evaluated.Results: Eighty-four patients were enrolled. In univariate analysis, pre-and post-HSCT PET findings were correlated with 3-year progression-free survival(PFS) [hazard ratio(HR)=4.391, P=0.001; HR=7.607, P<0.001] and overall survival(OS)(HR=4.792, P=0.008; HR=26.138, P<0.001). Patients receiving upfront auto-HSCT after firstline treatment had better outcomes than relapsed/refractory DLBCL patients(3-year PFS, P<0.001; 3-year OS,P<0.001). In the relapsed/refractory patients, pre-and post-HSCT PET findings were also associated with 3-year PFS(P=0.003 vs. P<0.001) and OS(P=0.027 vs. P<0.001). A significant correlation was observed between clinical response to chemotherapy before auto-HSCT and outcomes of patients in the entire cohort(3-year PFS, P<0.001;3-year OS, P<0.001) and in the subgroup of 21 patients with positive pre-HSCT PET(3-year PFS, P=0.084; 3-year OS, P=0.240). A significant association between survival and post-HSCT PET findings was observed in multivariate analysis(HR=5.168, P<0.001).Conclusions: PET results before and after HSCT are useful prognostic factors for DLBCL patients receiving HSCT. Patients who responded to chemotherapy, even those with positive pre-HSCT PET, are appropriate candidates for auto-HSCT.

Autologous transplantation of bone marrow mesenchymal stem cells on diabetic patients with lower limb ischemia

学习骨头髓的自体同源的移植的功效和安全的目的有更低的手足局部缺血的糖尿病的病人上的间充质的干细胞。有更低的手足局部缺血的五十种类型 2 糖尿病的病人被注册并且使随机化到也的方法移植了组或控制组。病人在两个都，组接受了一样的常规治疗。同时，从每个移植病人的 20 ml 骨头髓被收集，并且间充质的干细胞被密度坡度 centrifugation 分开并且在有自体同源的浆液的媒介有教养。在在 vitro 的三星期的支持者文化以后， 7.32 ????????????????? 金 ???????????? ㈠ ?????? ┷？

High-dose Chemotherapy Combined with Autologous Hematopoietic Stem Cell Transplantation as Frontline Therapy for Intermediate/High-risk Diffuse Large B Cell Lymphoma

The role of autologous hematopoietic stem cell transplantation(auto-HSCT)following high-dose chemotherapy has been validated and accepted as a standard treatment for patients with relapsed diffuse large B-cell lymphoma(DLBCL).However,its clinical efficacy as frontline therapy remains to be elucidated.This study aimed to examine the feasibility of frontline auto-HSCT for newly diagnosed intermediate/high-risk DLBCL patients.We retrospectively reviewed the data of 223 patients treated with frontline auto-HSCT or chemotherapy alone(year 2008-2014)from four hospitals.The median follow-up time was 29.4 months.Between the two treatment arms among the intermediate/high-risk DLBCL patients,the 3-year overall survival(OS)and progression-free survival(PFS)rates of patients given frontline auto-HSCT were 87.6%and 81.9%,respectively,and the chemotherapy-alone group showed 3-year OS and PFS rates of 64.9%and 59.59%,respectively.Compared with the chemotherapy-alone group,the frontline auto-HSCT could eliminate the adverse impact of non-germinal center B-cell(GCB)type.In addition,in the frontline auto-HSCT group,patients who achieved complete response(CR)at auto-HSCT had a longer survival time than those who did not achieve CR.Our results suggested that frontline auto-HSCT could improve the prognosis of intennediate/high-risk DLBCL patients.

Autologous hematopoietic stem cell transplantation for diabetic foot:A meta-analysis

Objective:To systematically evaluate the efficacy and safety of autologous hematopoietic stem cell(AHSCs)transplantation for diabetic foot(DF).Methods:A systematic search of literatures in PubMed,Embase,the Cochrane Library,CNKI,WanFang and VIP from inception to March 2020 was conducted.Clinical randomized controlled trials of AHSCs transplantation for DF were screened according to inclusion and exclusion criteria,and meta-analysis was performed using RevMan 5.3 software.Results:A total of 13 articles were included,including 582 patients within 292 received conventional treatment in the control group and 290 additionally received AHSCs in the transplantation group.Meta-analysis results showed that compared with the control group,the transplantation group improved ulcer healing rate[RR=2.38,95%CI(1.91,2.98),P<0.00001],ankle brachial index[MD=0.14,95%CI(0.11,0.16),P<0.00001]and skin temperature of injured limb[MD=1.39,95%CI(0.93,1.86),P<0.00001].And lowered mutation rate[RR=0.10,95%CI(0.04,0.26),P<0.00001],pain scores[MD=-1.37,95%CI(-1.62,-1.12),P<0.00001]and indirect claudication scores[MD=-0.89,95%CI(-1.04,-0.75),P<0.00001].The above differences were all statistically significant(P<0.05).Conclusion:Existing evidence shows that AHSCs transplantation for DF has certain clinical effects and safety.However,more high-quality research are needed to further demonstrate the above results.

Efficacy of peripheral blood stem cell transplantation versus conventional chemotherapy on anaplastic large-cell lymphoma:a retrospective study of 64 patients from a single center

Anaplastic large-cell lymphoma(ALCL) is characterized by frequently presenting adverse factors at diagnosis.Many groups believed aggressive treatment strategies such as autologous stem cell transplantation brought survival benefit for ALCL patients.However,few compared these approaches with conventional chemotherapy to validate their superiority.Here,we report a study comparing the efficacy of peripheral blood stem cell transplantation(PBSCT) and conventional chemotherapy on ALCL.A total of 64 patients with primary systemic ALCL were studied retrospectively.The median follow-up period was 51 months(range,1-167 months).For 48 patients undergoing conventional chemotherapy only,the 4-year event-free survival(EFS) and overall survival(OS) rates were 70.7% and 88.3%,respectively.Altogether,16 patients underwent PBSCT,including 11 at first remission(CR1/PR1),3 at second remission,and 2 with disease progression during first-line chemotherapy.The 4-year EFS and OS rates for patients underwent PBSCT at first remission were 81.8% and 90.9%,respectively.Compared with conventional chemotherapy,PBSCT did not show superiority either in EFS(P = 0.240) or in OS(P = 0.580) when applied at first remission.Univariate analysis showed that patients with B symptoms(P = 0.001),stage III/IV disease(P = 0.008),bulky disease(P = 0.075),negative anaplastic lymphoma kinase(ALK) expression(P = 0.059),and age ≤ 60 years(P = 0.054) had lower EFS.Furthermore,PBSCT significantly improved EFS in patients with B symptoms(100% vs.50.8%,P = 0.027) or bulky disease(100% vs.52.8%,P = 0.045) when applied as an up-front strategy.Based on these results,we conclude that,for patients with specific adverse factors such as B symptoms and bulky disease,PBSCT was superior to conventional chemotherapy in terms of EFS.

AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR LYMPHOMA: AN EVALUATION OF GRAFTS SOURCE AND MINIMAL RESIDUAL DISEASE

Objective： To determine whether the source of autologous hematopoietic stem cells altered the clinical outcomes of patients undergoing high dose chemotherapy and autologous hematopoietic stem cell transplantation （AHSCT） for aggressive lymphoma and to study the problem of minimal residual disease （MRD）. Methods： 14 lymphoma patients who had lymphoma with high risk factors, relapsed lymphoma or refractory lymphoma received autologous bone marrow transplantation （ABMT）. 14 lymphoma patients who were similar to ABMT group received autologous peripheral blood stem cells transplantation （APBSCT）. Regimen of CBV （cyclophos phamide 50-60 mg/kg/d×2 d, carmustine 15 mg/kg/d×1 d, etoposide 45-60 mg/kg/d×1 d） was received by all the patients as conditioning regimen in the transplant pretreatment followed by ABMT or APBSCT. Autologous peripheral blood stem cell （APBSC） was mobilized by CTX 2g-3g/m^2/d×2 d iv and G-CSF 5 μg/kg/d for five to seven days. MRD was continually supervised by PCR in bone marrow before and after transplantation. Cellular immunocyte function, such as natural killer cell （NK）, CD3, CD4, CD8 and slL-2R was tested before and twenty days after transplantation. Results： In ABMT group, the median time for hematopoietic recovery of absolute neutrophilia counts ≥0.5×10^9/L and platelet counts ≥20×10^9/L. was ＋18 days and ＋20 days respectively. In contrast, the APBSCT group was both at 12 days. Patients who have undergone ABMT all got complete remission （CR）, while 81.8% patients in APBSCT group got CR. The 3-year disease free survival （DFS） in APBSCT and ABMT group was 75% and 72.7% respectively （P〉0.05）. The mean days of immunity recovering in APBSCT was ＋20 days. After transplantation, MRD in 11 patients were positive, in whom 6 patients died. Conclusion： Aggressive lymphoma patients＇ hemapoiesis recovered more rapidly in APBSCT group than that in ABMT group, but 3-year DFS had no statistical difference. Patients positive for IgH/TCR-γ by molecular PCR analysis had poor DFS. Molecur monitoring of MRD using PCR techniques seems to represent a reliable prognostic indicator. Immunotherapy in the patients whose bone morrow was positive for MRD post-AHSCT may intensify remission and reduce relapse rates.

THE PRELIMINARY RESULTS OF TREATMENT OFADVANCED AND RECURRENT MALIGNANT LYMPHOMA BY BEAC REGIMEN SUPPORTED WITH AUTOLOGOUS HEMATOPOIETIC STEM CELLS TRANSPLANTATION

Objective: High dose chemotherapy supported by autologous hematopoietic stem cells transplantation (AHSCT) has developed dramaticly in recent years and become the most effective approach to improve radical treatment for the chemo-sensitive lymphoma. The purposes of this study was to evaluate the efficacy and tolerance of preparative regimen BEAC and hematopoietic reconsti- tution after high dose chemotherapy in Chinese patients with advanced and recurrent lymphoma. Methods: After confirmed complete or partial remission from conventional chemotherapy, 24 patients with advanced or recurrent lymphoma including 1 recurrent HD and 23 NHL, 16 male and 8 female with median age of 29 (13-50) years, were enrolled into this study and treated by BEAC regimen (CTX 3600-4000 mg/m2, VP-16 1200 mg/m2. BCNU 300 mg/m2 and Ara-C 1500-2000 mg/m2). 3 patients were supported by ABMT and 21 by APBSCT. Mobilization regimen for APBSCT was CTX 3500 mg/m2 + G-CSF 3.5-5 mg/kg + Dexamethasone 10 mg. Autologous hematopoietic stem cells was re-infused 24-48 h after completion of high dose chemotherapy. Results: MNC 1.3 (1.0-1.7) 108/kg and MNC 1.8 (1.0-4.4) 108, CFU-GM 5.1 (1.9-9.6) 105/kg plus CD34 + cells 2.9 (1.9-8.7) 106/kg were re-infused in the ABMT group and APBSCT group respectively. All patients obtained prompt and sustained hematopoietic reconstitution. ANC 0.5 109/L and Pt 2.0 109/L were at day 9 (6-17) and day 10 (0-31) respectively. 16 patients were alive with median 21 (2-69) months follow-up till end of May, 2001. 1, 2 and 3 years survival rate were 60.5%, 50.1% and 50.1%, respectively. Non-hematologic toxicity was mild and tolerable. Conclusions: High dose chemotherapy supported by AHSCT in the treatment of previously-untreated poor- prognostic and recurrent lymphoma was a safe and effective modality. Further investigation was warranted.

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.

How old is too old? In vivo engraftment of human peripheral blood stem cells cryopreserved for up to 18 years-implications for clinical transplantation and stability programs

BACKGROUND Peripheral blood stem cells(PBSC)are commonly cryopreserved awaiting clinical use for hematopoietic stem cell transplant.Long term cryopreservation is commonly defined as five years or longer,and limited data exists regarding how long PBSC can be cryopreserved and retain the ability to successfully engraft.Clinical programs,stem cell banks,and regulatory and accrediting agencies interested in product stability would benefit from such data.Thus,we assessed recovery and colony forming ability of PBSC following long-term cryopreservation as well as their ability to engraft in NOD/SCID/IL-2 Rγnull(NSG)mice.AIM To investigate the in vivo engraftment potential of long-term cryopreserved PBSC units.METHODS PBSC units which were collected and frozen using validated clinical protocols were obtained for research use from the Cellular Therapy Laboratory at Indiana University Health.These units were thawed in the Cellular Therapy Laboratory using clinical standards of practice,and the pre-freeze and post-thaw characteristics of the units were compared.Progenitor function was assessed using standard colony-forming assays.CD34-selected cells were transplanted into immunodeficient mice to assess stem cell function.RESULTS Ten PBSC units with mean of 17 years in cryopreservation(range 13.6-18.3 years)demonstrated a mean total cell recovery of 88%±12%(range 68%-110%)and post-thaw viability of 69%±17%(range 34%-86%).BFU-E growth was shown in 9 of 10 units and CFU-GM growth in 7 of 10 units post-thaw.Immunodeficient mice were transplanted with CD34-selected cells from four randomly chosen PBSC units.All mice demonstrated long-term engraftment at 12 wk with mean34%±24%human CD45+cells,and differentiation with presence of human CD19+,CD3+and CD33+cells.Harvested bone marrow from all mice demonstrated growth of erythroid and myeloid colonies.CONCLUSION We demonstrated engraftment of clinically-collected and thawed PBSC following cryopreservation up to 18 years in NSG mice,signifying likely successful clinical transplantation of PBSC following long-term cryopreservation.