Journal of hematotherapy最新文献

{"title":"Interferon as maintenance therapy in refractory malignant lymphoma.","authors":"A Avilés,&nbsp;A Talavera,&nbsp;N R Díaz,&nbsp;N Neri","doi":"10.1089/106161299320280","DOIUrl":"https://doi.org/10.1089/106161299320280","url":null,"abstract":"<p><p>Patients with refractory malignant lymphoma (RML) have a poor prognosis when treated with conventional chemotherapy, as less than 20% remain alive and free of disease after 5 years. The use of myeloablative chemotherapy followed by BMT has improved the complete remission (CR) rate. Nevertheless, relapse rates remain unchanged, and only a few patients remain alive and free of disease for more than 3 years. For this reason, we began a prospective randomized clinical trial to determine if IFN-alpha2B (5.0 MU three times a week for 1 year) can improve the prognosis in RML. Ninety-six patients with high or high-intermediate clinical risk RML and in CR after intensive chemotherapy were randomly assigned to receive or not to receive IFN as maintenance therapy. A median follow-up of 48.1 months, the time to treatment failure and survival were similar in both groups. Toxicity secondary to IFN administration was mild, and all patients received the planned doses of IFN. We conclude that IFN is not recommended at this dose and schedule as maintenance therapy in patients with RML who achieve CR. Different therapeutic approaches may be developed to improve outcomes for these patients.</p>","PeriodicalId":77208,"journal":{"name":"Journal of hematotherapy","volume":"8 3","pages":"263-7"},"PeriodicalIF":0.0,"publicationDate":"1999-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/106161299320280","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21282069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum granulocyte colony-stimulating factor kinetics in children receiving intense chemotherapy with or without stem cell support.","authors":"S Saito,&nbsp;Y Kawano,&nbsp;T Watanabe,&nbsp;Y Okamoto,&nbsp;T Abe,&nbsp;Y Kurada,&nbsp;Y Takaue","doi":"10.1089/106161299320325","DOIUrl":"https://doi.org/10.1089/106161299320325","url":null,"abstract":"<p><p>In a previous study, we speculated that the early phase of hematopoietic recovery after PBSC transplantation (PBSCT) is rapid because of the increased production of endogenous cytokines by co-transfused monocytes and lymphocytes (Kawano Y, et al. Blood 81:856, 1993). To clarify this point, the serum level of G-CSF was measured using an ELISA, and various other cytokines, including GM-CSF, macrophage-CSF (M-CSF), SCF, IL-6, IFN-gamma, and soluble IL-2 receptor (IL-2R), were tested for comparison in children receiving conventional or high-dose chemotherapy and autologous transplantation with unmanipulated or purified PBSC. Serum G-CSF levels in patients receiving conventional chemotherapy (n = 21) or PBSCT without exogenous G-CSF treatment (n = 19) increased to 1245 +/- 2337 pg/ml and 2741 +/- 2331 pg/ml, respectively. Likewise, the peak level of G-CSF in patients who did not receive G-CSF was statistically equivalent to the trough level in those who did. There was no significant difference in the speed of hematopoietic recovery with or without G-CSF treatment in both the conventional chemotherapy and PBSCT cohorts. In addition, no meaningful change was observed in the kinetics of other tested factors in either conventional therapy or PBSCT settings, regardless of whether the patient did or did not receive G-CSF. Endogenously produced serum peak G-CSF levels after PBSCT with purified CD34+ cells were identical to those after the same procedure with unmanipulated cells. These results confirm that children receiving intense chemotherapy followed by autologous PBSCT produce a high level of G-CSF during the cytopenic period that is not due to the infusion of a large amount of facilitating cells capable of producing G-CSF.</p>","PeriodicalId":77208,"journal":{"name":"Journal of hematotherapy","volume":"8 3","pages":"291-7"},"PeriodicalIF":0.0,"publicationDate":"1999-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/106161299320325","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21283200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanding mobilized progenitors for hematotherapy.","authors":"D English","doi":"10.1089/106161299320361","DOIUrl":"https://doi.org/10.1089/106161299320361","url":null,"abstract":"","PeriodicalId":77208,"journal":{"name":"Journal of hematotherapy","volume":"8 2","pages":"91-2"},"PeriodicalIF":0.0,"publicationDate":"1999-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/106161299320361","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21219125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"G-CSF-mobilized leukapheresis products: cellular characteristics and clinical performance in allografting.","authors":"D Dłubek,&nbsp;T Pacuszko,&nbsp;K Suchnicki,&nbsp;A Lange","doi":"10.1089/106161299320424","DOIUrl":"https://doi.org/10.1089/106161299320424","url":null,"abstract":"<p><p>Twenty-five G-CSF-mobilized leukapheresis products (mLP) were screened for cellular composition, including CD34+DR-, CD34+DR+ and leukocyte profile, to compare with 5 native (unstimulated) LP (nLP) and 16 BM inoculi. G-CSF stimulation led to an increase in CD34+ cells and CD15+ cells but did not influence the lymphocyte content of mLP. Two groups of 14 and 16 patients were allografted with phenotypically defined mLP (1-4 mLP were used for each patient) and BM, respectively. mLP used for allografting had significantly more CD34+ cells, including CD34+DR- cells, monocytes, T cells, and B cells as compared with BM inoculi. Patients were followed for median observation time of 289 days and 409 days for the mLP (PBPC) and BM groups, respectively. The two groups were well matched in regard to age, sex, and stage of disease, with a slight prevalence of major blood group incompatibility (7 of 14 versus 3 of 16) and a lower donor/recipient weight ratio (0.8+/-0.2 vs 1.5+/-0.6, p = 0.002) in the PBPC group. Granulocyte and platelet recovery was faster in the PBPC group than in the BM group. The time of reaching 20,000/microl platelets but not 500/microl granulocytes correlated with the number of CD34+ cells in each inoculum. The survival curves of the PBPC and BM groups were similar, as was the incidence of acute GvHD (aGvHD). This was also valid for aplastic anemia cases (7 and 5 patients in the PBPC and BM group, respectively), who benefited from a high number of CD34+ grafted cells but did not experience aGvHD. Thus, mLP do not appear to elicit aGvHD with higher frequency than BM and may be preferable for hematotherapy.</p>","PeriodicalId":77208,"journal":{"name":"Journal of hematotherapy","volume":"8 2","pages":"157-66"},"PeriodicalIF":0.0,"publicationDate":"1999-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/106161299320424","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21219131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of merocyanine 540 for the isolation of quiescent, primitive human bone marrow hematopoietic progenitor cells.","authors":"R E Pyatt,&nbsp;L L Jenski,&nbsp;R Allen,&nbsp;K Cornetta,&nbsp;R Abonour,&nbsp;C M Traycoff,&nbsp;E F Srour","doi":"10.1089/106161299320460","DOIUrl":"https://doi.org/10.1089/106161299320460","url":null,"abstract":"<p><p>Merocyanine 540 (MC540) is a membrane probe that inserts preferentially into loosely packed domains in the phospholipid bilayer of intact cells. Previous experiments have demonstrated that MC540 will bind to human bone marrow (BM) hematopoietic progenitor cells (HPC). Fractions of mononuclear BM cells expressing high MC540 fluorescence have been shown to be enriched for myeloid progenitors and cells residing in the S/G2 + M phases of the cell cycle. We rationalized that MC540 uptake could be used to distinguish between quiescent and metabolically active cells and, therefore, to fractionate normal and leukemic BM cells and normal mobilized peripheral blood (MPB) cells into functionally distinct groups of progenitors. BM and MPB cells were separated into fractions ranging in fluorescence from MC540Bright to MC540Dim. Cell cycle analysis of these fractions revealed that the MC540Dim fraction of normal and CML BM CD34+ cells constituted the most quiescent fraction, and the MC540Bright fractions from these cell types contained the most actively cycling cells. However, no differences in the percentage of cells in G/G1 were observed between MC540Bright and MC540Dim fractions of MPB CD34+ cells. To investigate if these cell cycle status differences translated into distinct functional properties, the hematopoietic potential of BM CD34+MC540Bright and CD34+MC540Dim cell fractions was analyzed in vitro in long-term BM cultures and limiting dilution analysis (LDA) assays. CD34+MC540Dim cells produced more total and committed progenitor cells in long-term cultures than did the CD34+MC540Bright fraction. The CD34+MC540Dim fraction also contained a 2-fold higher number of long-term hematopoietic culture-initiating cells (LTHCIC) than the CD34+MC540Bright fraction, as defined by LDA assays. These data demonstrate that MC540 can be a useful probe for the isolation of primitive HPC from some hematopoietic tissues and may assist in monitoring structural changes in the phospholipid bilayer during proliferation and differentiation of HPC.</p>","PeriodicalId":77208,"journal":{"name":"Journal of hematotherapy","volume":"8 2","pages":"189-98"},"PeriodicalIF":0.0,"publicationDate":"1999-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/106161299320460","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21219815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ex vivo expansion of hematopoietic stem and progenitor cells: are we there yet?","authors":"E F Srour,&nbsp;R Abonour,&nbsp;K Cornetta,&nbsp;C M Traycoff","doi":"10.1089/106161299320370","DOIUrl":"https://doi.org/10.1089/106161299320370","url":null,"abstract":"<p><p>Ex vivo expansion of hematopoietic stem and progenitor cells is a very ambitious idea that would have major implications in the areas of stem cell transplantation and somatic gene therapy. However, successful ex vivo expansion has evaded and frustrated scientists for a number of years. The goal of ex vivo expansion is to induce cell division and proliferation of stem cells while maintaining their primary functional characteristic, namely, their ability to engraft and sustain long-term hematopoiesis. Only when a balance between these two requirements is reached can ex vivo expansion of stem cells be considered successful. Establishing such a balance has not been easy. However, many lessons have been learned along the way, and today we have a more profound understanding of the potential obstacles facing ex vivo expansion than we did only a few years ago. In this review, we discuss these obstacles and evaluate the current status of ex vivo expansion of stem and progenitor cells both from the perspective of basic stem cell biology and from the viewpoint of clinical utility of these cells in transplantation.</p>","PeriodicalId":77208,"journal":{"name":"Journal of hematotherapy","volume":"8 2","pages":"93-102"},"PeriodicalIF":0.0,"publicationDate":"1999-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/106161299320370","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21219126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fetal cord blood as an alternative source of hematopoietic progenitor cells: immunophenotype, maternal cell contamination, and ex vivo expansion.","authors":"H Engel,&nbsp;E Kaya,&nbsp;R Bald,&nbsp;H Kolhagen,&nbsp;O Grecu,&nbsp;T Schöndorf,&nbsp;U Brenne,&nbsp;C M Kurbacher,&nbsp;U J Göhring,&nbsp;M Kleine,&nbsp;P Mallmann","doi":"10.1089/106161299320415","DOIUrl":"https://doi.org/10.1089/106161299320415","url":null,"abstract":"<p><p>The present study was performed to investigate the character of hematopoietic progenitor cells in fetal cord blood (CB). Thirty blood samples from fetuses at a median of 24 weeks of gestation (range 19-29) and 30 neonatal CB samples were analyzed for their immunophenotype by three-color flow cytometry and examined for the presence of female cells by fluorescence in situ hybridization (FISH). We tested the effects of different cytokine combinations (rhIL-1beta, rhIL-3, rhIL-6, rh erythropoietin [rhEPO], rhGM-CSF plus rhSCF, and rhSCF plus rhflt3-ligand) on the differentiation of 100 CD34+-enriched neonatal CB cells for up to 21 days. Ex vivo expansion of 32 unselected fetal blood samples cells was performed in the presence of rhSCF and rhflt3-ligand. The percentage of CD34+ cells in fetal blood was significantly higher compared with neonatal CB (1.24%+/-0.82% versus 0.33%+/-0.18%, p = 0.0001) and inversely correlated with the age of gestation. The contamination of fetal and neonatal CB with maternal cells was low (1.72%+/-0.89%, range 1.0%-4.0%). By using rhflt3-ligand we were able to expand committed progenitor cells while maintaining cells with stem cell function. The use of expanded fetal immature progenitors might have implications for in utero transplantation and autologous gene therapy.</p>","PeriodicalId":77208,"journal":{"name":"Journal of hematotherapy","volume":"8 2","pages":"141-55"},"PeriodicalIF":0.0,"publicationDate":"1999-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/106161299320415","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21219130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Successful PBSC mobilization with high-dose G-CSF for patients failing a first round of mobilization.","authors":"Y Gazitt,&nbsp;C O Freytes,&nbsp;N Callander,&nbsp;T W Tsai,&nbsp;M Alsina,&nbsp;J Anderson,&nbsp;L Holle,&nbsp;J Cruz,&nbsp;P Devore,&nbsp;M McGrath,&nbsp;G West,&nbsp;R Alvarez,&nbsp;W Montgomery","doi":"10.1089/106161299320442","DOIUrl":"https://doi.org/10.1089/106161299320442","url":null,"abstract":"<p><p>PBSC are the preferred source of stem cells for autologous transplantation. However, regardless of the mobilization procedure used, 10%-20% of patients fail to collect an adequate number to ensure prompt engraftment. There is as yet no standard mobilization procedure for patients who fail a first mobilization attempt. Here, we describe a highly efficient strategy to obtain an adequate number of stem cells for patients who failed a first mobilization attempt. Seventy-four patients with various hematologic malignancies underwent initial mobilization with various regimens including hematopoietic growth factors with or without chemotherapy. In 72% of patients, > or =2 x 10(6) CD34+ stem cells/kg were collected in the initial mobilization attempt, and patients engrafted in a median of 10 days for neutrophils and 12 days for platelets. Eighteen patients failed to mobilize adequate numbers of stem cells, defined as the inability to collect 0.2 x 10(6) CD34+ stem cells/kg/day in the first 2-3 days. These patients had their apheresis halted. Patients were immediately given G-CSF (32 microg/kg/day) for 4 days as a second attempt at mobilization. Eighty-eight percent of these patients achieved the target of > or =2 x 10(6) CD34+ cells/kg, with a median duration of apheresis of 5 days (including the first and second mobilizations). The mean CD34+ cells/kg/day increased after administration of high-dose G-CSF from 0.16 after the first mobilization attempt to 0.61 (p = 0.0002) after the second mobilization. All patients engrafted in a median of 11 and 13 days for neutrophils and platelets, respectively. We conclude that patients whose apheresis yield is <0.4 x 10(6) CD34+ cells/kg after the first two apheresis collections can be successfully mobilized if high-dose G-CSF is administered immediately and continued until achieving > or =2 x 10(6) CD34+ stem cells/kg.</p>","PeriodicalId":77208,"journal":{"name":"Journal of hematotherapy","volume":"8 2","pages":"173-83"},"PeriodicalIF":0.0,"publicationDate":"1999-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/106161299320442","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21219133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The relation between the number of PBSC and number of leukaphereses in children.","authors":"T Kajiume,&nbsp;S Yoshimi,&nbsp;K Kobayashi,&nbsp;N Kataoka","doi":"10.1089/106161299320451","DOIUrl":"https://doi.org/10.1089/106161299320451","url":null,"abstract":"<p><p>Although PBSC transplantation has an advantage over BM transplantation in that fewer burdens are placed on the patient at the time of stem cell collection, the number of collected cells decreases when leukapheresis is done repeatedly. We examined the relation between the number of times leukapheresis is performed and the number of mononuclear cells (MNC), CD34+ cells, and colony-forming unit-granulocyte-macrophages (CFU-GM) collected. The percentage of CD34+ cells was measured by flow cytometry and the number of CFU-GM was measured by a progenitor assay. The number of cells collected was significantly decreased by the third collection. Therefore, to secure enough cells for transplantation, leukapheresis ideally should be performed no more than twice if PBSC collection is to be efficient.</p>","PeriodicalId":77208,"journal":{"name":"Journal of hematotherapy","volume":"8 2","pages":"185-8"},"PeriodicalIF":0.0,"publicationDate":"1999-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/106161299320451","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21219814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical scale expansion of cryopreserved small volume whole bone marrow aspirates produces sufficient cells for clinical use.","authors":"B I Lundell,&nbsp;R K Mandalam,&nbsp;A K Smith","doi":"10.1089/106161299320398","DOIUrl":"https://doi.org/10.1089/106161299320398","url":null,"abstract":"<p><p>Ex vivo expansion of bone marrow (BM) mononuclear cells (MNC) in a perfused culture system produces stem-progenitor cell type(s) in sufficient number(s) for hematopoietic reconstitution. The limitations in using fresh BM MNC for ex vivo expansion include additional cell processing and inflexibility in patient treatment. Cryopreservation of whole bone marrow (WBM) eliminates processing costs of MNC or CD34+ cell selection and allows for flexibility in patient treatment. We developed a convenient system to cryopreserve and thaw small volume WBM aspirations (n = 13) and then compared the expandability of unprocessed normal cryopreserved/thawed (C/T) WBM to that of fresh BM MNC cultured in the presence of erythropoietin, PIXY 321, and Flt3-ligand. Ex vivo expansion potential was retained in WBM aspirates after C/T. When initiated with 225 million viable nucleated cells, clinical scale expansion cultures (n = 6) yielded 9.7+/-2.8 x 10(8) total cells, which contained 10.4+/-5.8 x 10(6) colony-forming units-granulocyte-macrophage (CFU-GM), 1.3+/-1.4 x 10(4) LTCIC, and 2.2 x 10(6) CD34+Lin- cells, sufficient cell numbers for clinical use. These studies demonstrate that ex vivo perfusion culture expansion of unfractionated C/T WBM (< or =30 ml) provides doses of stem-progenitor cells similar in composition to expanded fresh BM MNC, previously demonstrated to achieve hematopoietic reconstitution.</p>","PeriodicalId":77208,"journal":{"name":"Journal of hematotherapy","volume":"8 2","pages":"115-27"},"PeriodicalIF":0.0,"publicationDate":"1999-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/106161299320398","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21219128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}