ISSN:1066-5099    

DOI:10.1002/stem.5530110902

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractSome patients with Philadelphia (Ph) hromosome‐positive chronic myeloid leukemia CML) may achieve partially or completely Ph‐negtive hemopoiesis after treatment with high doses of ytotoxic drugs or interferon‐α at standard dosage. This observation leads to three important questions: 1) are Ph‐negative myeloid cells in such patients strictly normal? 2) can such Ph‐negative ells be identified in all newly diagnosed patients or only in a minority? and 3) what is the basis for he proliferative advantage manifested by CML ells and why might it be temporarily lost as a result of treatment? The mechanisms that might prevent he proliferation of normal cells in an environment of Ph‐positive cells and the relevance of these questions to the design of a strategy aimed at obtaining complete remission in the majority of patients are considered. Such a strategy might incorporate auto‐grafting with Ph‐negative stem cells harvested during the recovery phase of high d

ISSN:1066-5099    

DOI:10.1002/stem.5530110903

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

ISSN:1066-5099    

DOI:10.1002/stem.5530110904

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractDonor marrow transplantation can cure chronic myelogenous leukemia (CML). Unfortunately, the procedure is associated with severe complications and is limited to the minority of potential recipients with suitably matched donors. Autologous marrow transplantation using negative selection approaches such as incubation with gamma interferon (IFN‐γ) can produce cytogenetic and clinical remissions, but they are often associated with recurrent evidence of leukemia. A primitive progenitor population can be separated from normal human marrow on the basis of morphologic characteristics and cell surface antigen expression. Cell populations with similar morphologic and phenotypic characteristics obtained by positive selection from the marrow of patients with CML appear to be benign. Benign primitive and committed progenitors selected in this fashion can be expanded ex vivo when cultured in a “Transwell” system which physically separates hematopoietic cells from stromal feeder layers. Positive selection and ex vivo cultivation of benign progenitors from CML marrow may provide a source of hematopoietic stem cells suitable for autologous marrow transplantation. Autologous natural killer (NK) cells obtained from the peripheral blood of patients with CML are of benign origin and have antileukemia activity. Interleukin 2 (IL‐2) activated autologous NK cells may be used in post‐transplant cellular therapy to prevent recurre

ISSN:1066-5099    

DOI:10.1002/stem.5530110905

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractAllogeneic bone marrow transplantation (BMT) is a useful approach for treating patients with chronic myelogenous leukemia (CML). In patients who lack a suitable donor, various approaches to utilize the patient's own hematopoietic stem cells obtained from bone marrow and/or peripheral blood have been developed. Preferential recovery of normal human hematopoietic progenitors over CML clone in long‐term bone marrow culture (LTBMC) has been observed for a long time. LTBMC initiated in tissue culture (TC) flasks to that in “Lifecell” bags, which are gas‐permeable plastic bags in which feeder‐layer cells cannot adhere, has been investigated for several years. In our laboratory, cells were incubated in the presence of various growth factors to develop improved methods for stem cell expansion. Sustained hematopoietic stem cell growth in the absence of a feeder layer in plastic gas‐permeable bags has been observed. Growth of marrow from patients with CML is being investigated extensively. Combining effective drugs to decrease the Philadelphia (Ph) clone prior to bone marrow harvest and the use of cultured bone marrow may provide a useful method for treating patients with CML. Results of various international studies are also disc

ISSN:1066-5099    

DOI:10.1002/stem.5530110906

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractThe optimal approach for curing patients with chronic myeloid leukemia (CML) in chronic phase (CP) is an allogeneic bone marrow transplant BMT). However, this approach is not available to he majority of patients. Autografting, using either burged or unpurged bone marrow or peripheral blood stem cells (PBSC), could be beneficial for patients who are not eligible for BMT. Between 1984 and 1992, 21 patients with CML in CP were auto‐grafted using unmanipulated PBSC harvested either at diagnosis or thereafter. Ten of 21 patients survived at a median of 84 months following auto‐grafting (range: 12–108 months). Eleven patients lied, seven of blast transformation and four from other causes. The timing of the autograft or the harvest does not appear to have a bearing on sur

ISSN:1066-5099    

DOI:10.1002/stem.5530110907

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

ISSN:1066-5099    

DOI:10.1002/stem.5530110908

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractTen adult patients with Ph‐positive chronic myelogenous leukemia (CML) received autologous bone marrow transplantation (ABMT) using marrow treated ex vivo with mafosfamide. At the time of ABMT, six patients were in chronic phase and four in accelerated phase. Seven of ten patients reported herein were selected on the basis of a previous laboratory assessment of the numbers of normal and leukemic stroma‐adherent progenitor cells within mafosfamide‐treated marrow. Only patients showing ≥50% Ph‐negative stroma‐adherent progenitor cells within mafosfamide‐treated marrow were considered eligible for autografting. In nine out of ten evaluable patients, the median time to achieve 500 neutrophils/μl was 32 days (range: 25–72). A platelet count of 2 × 104/μl was achieved at a median of 40 days (range: 27–97). Six out of nine analyzable patients engrafted Ph‐negative. The median duration of the Ph‐negative hematopoiesis, confirmed also by Southern blot analysis, was 6.5 months (range: 4–30). A good correlation was evident between the results of the in vitro preharvest screening test and the in vivo occurrence of normal hematopoiesis post‐transplant. Two patients who showed 75% and 89% Ph‐negative stroma‐adherent progenitors engrafted Ph‐positive, whereas four out of five evaluable patients who had 100% Ph‐negative stroma‐adherent progenitors engrafted Ph‐negative. After a median follow‐up of 16 months (range: 3–31), five patients evolved into blast crisis, three are alive in hematologic and cytogenetic relapse, and one died without evolving into blast crisis. In conclusion, our results demonstrate that: 1) engraftment can occur from Ph‐negative stem cells selected by mafosfamide purging; 2) in selected CML patients, mafosfamide is effective in reducing the size of the malignant clone and inducing a transient period of Ph‐negative hematopoiesis; and 3) modifications of the purging procedure as well as post‐transplant manipulation of the immune‐hematopoietic system are required to prolong cytogenetic remission or cure CML patients ineligible for allog

ISSN:1066-5099    

DOI:10.1002/stem.5530110909

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractIt is now feasible to investigatebcr‐abltranscription by the progeny of Ph‐positive (Ph+) early and committed hemopoietic progenitor cells from patients with chronic myeloid leukemia (CML). Cells from individual colonies can be bisected and each half analyzed by cytogenetics or the reverse transcriptase‐polymerase chain reaction (RT‐PCR) method to detect thebcr‐abltranscript using internal nested oligonucleotide primers that flank the chimeric gene junction. We previously showed that some Ph+colonies have undetectable PCR products forbcr‐abl.When colonies are generated in the presence of alpha interferon (IFN‐α)bcr‐abltranscripts are undetectable in the majority of Ph+colonies. These data suggest a potential mechanism for the action of IFN‐α in Ph+CML and indicate the need for a combined approach with cytogenetics and RT‐PCR in ana

ISSN:1066-5099    

DOI:10.1002/stem.5530110910

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractPatients with chronic myelogenous leukemia (CML) can be cured with allogeneic bone marrow transplantation. Over the past decade, it has become clear that immunological mechanisms, in the form of graft‐versusleukemia, constitute an integral part of this therapy. Because of limitations imposed by a lack of suitable donors, age, and toxicity, only a minority of patients can be offered allogeneic bone marrow transplantation (BMT). Recently, attempts have been made to employ autologous bone marrow transplantation (ABMT) for the therapy of CML using a variety of pre‐ and post‐transplantation manipulations. This report describes the rationale for an ongoing clinical trial using the immunomodulator roquinimex (Linomide), following autologous bone marrow transplantation, in an attempt to stimulate the immunological responses thought to be critical for successful therapy i

ISSN:1066-5099    

DOI:10.1002/stem.5530110911

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY