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Results for “Bone Marrow Purging”

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At least 991 records · Page 55Linked to original sources
PubMed1996

High-dose therapy and autologous bone marrow transplantation in patients with follicular lymphoma during first remission.

We report the results of a study in previously untreated advanced stage patients with follicular lymphoma (FL) who underwent uniform induction chemotherapy with cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) followed by myeloablative therapy and anti-B-cell monoclonal antibody purged autologous bone marrow transplantation (ABMT). Eighty-three patients with previously untreated, low-grade FL were enrolled. After CHOP induction, only 36% achieved complete remission (CR) and 77 patients underwent ABMT. Before BM harvest, 70 patients had a known t(14;18), as determined by polymerase chain reaction (PCR), and all remained PCR positive in the BM at harvest. After ABMT, the disease-free survival (DFS) and overall survival are estimated to be 63% and 89% at 3 years, respectively, with a median follow-up of 45 months. Patients whose BM was PCR negative after purging experienced significantly longer freedom from recurrence (FFR) than those whose BM remained PCR positive (P = .0006). Continued PCR negativity in follow-up BM samples was also strongly predictive of continued CR. This study suggests that a subset of patients with advanced FL may experience prolonged clinical and molecular remissions following high-dose ablative therapy, although longer follow-up will be necessary to determine potential impact on overall survival.

Adult↗
PubMedDate not supplied

[The identification of minimal residual disease in the bone marrow and peripheral blood in neuroblastoma. The prognostic and therapeutic implications].

A highly sensitive and specific methodology to detect neuroblastoma cells in the bone marrow and peripheral blood of children with neuroblastoma is of critical importance for proper staging and treatment of these patients. In addition, patients with bone marrow infiltration at diagnosis need to undergo regular investigation to measure the effectiveness of chemotherapy (so called "in vivo" purging). Finally, the evaluation of autologous stem cells taken from bone marrow or peripheral blood is necessary to rule out or minimise the possibility of reinfusing tumor cells to the patient following myeloablative therapy. The authors provide a "state of the art" data on this complicated issue and give their preliminary results of their own experience, mainly concerning the immunocytological methods.

Biomarkers, Tumor↗
PubMed1994

Characterization of murine and humanized anti-CD33, gelonin immunotoxins reactive against myeloid leukemias.

M195 antibodies recognize CD33, an antigen present on acute myeloid leukemia blasts as well as some myeloid progenitor cells, but not on the ultimate hematopoietic progenitor stem cell. Immunotoxins (IT) reactive with human myeloid leukemias were constructed by conjugating gelonin, a single-chain ribosome-inactivating protein, to murine and genetically engineered, humanized M195 antibodies via an N-succinimidyl-3-(2-pyridyl-dithio)-propionate linkage. No losses of gelonin cytotoxic activity or M195 binding activity were observed after conjugation of up to two toxin molecules per antibody. Toxin conjugates displayed specific, potent toxicity for CD33+ cells. The murine and humanized IT were not toxic to CD33- cells and were 600 and 4500 times more potent, respectively, than free gelonin in inhibiting CD33+ HL60 cells. Treatment of HL60 cells with 1 micrograms/ml HuM195-gelonin resulted in more than 1000 times lower colony formation; normal bone marrow mononuclear cell colony-forming units treated with HuM195-IT were reduced by a factor of 10. HL60 leukemia cells could be effectively purged from an excess of normal bone marrow cells. Exposure of target cells to IT for as little as 30 min was as effective as continuous exposure of IT for up to 6 days. However, measures of the efficacy of the immunotoxin were directly related to the length of time of observation after IT exposure and were inversely related to cell concentration. M195-gelonin immunoconjugates are potential candidates for therapeutic use in in vivo or ex vivo bone marrow purging for myeloid leukemias.

Animals↗
PubMed2004

Ex-vivo purging of hematopoietic progenitor cells.

High-dose chemoradiation therapy with autologous hematopoietic progenitor cell support is effective treatment for patients with a variety of high-risk malignancies. In this setting, tumor cell contamination of the hematopoietic progenitor cell product is a frequently observed problem. The malignant cells in the autograft may be a source of relapse after transplant. Purging the hematopoietic cell grafts ex-vivo may eradicate malignant cells that may contaminate the autologous product. This chapter describes the major purging strategies that have been investigated clinically over the past decade. This investigation includes negative purging with pharmacologic agents and monoclonal antibodies, positive selection with immunoadsorption, immunomagnetic and flow cytometric sorting techniques, ex-vivo culture method, treatment with cytotoxic T cells, and virally mediated purging methods.

Antineoplastic Agents↗
PubMed1999

Autologous bone marrow transplantation after histologic transformation of indolent B cell malignancies.

The role of high-dose therapy and autologous stem cell transplantation in diffuse large B cell lymphoma (DLBCL) after transformation is controversial. We have retrospectively analyzed patients with chemosensitive disease and a history of follicular lymphoma or chronic lymphocytic leukemia/small lymphocytic lymphoma who underwent high-dose chemoradiotherapy and bone marrow transplantation (BMT) with anti-B cell monoclonal antibody-purged autologous marrow for DLBCL. Between December 1982 and August 1997, 27 patients underwent autologous BMT using a uniform ablative regimen with cyclophosphamide, total-body irradiation, and bone marrow purging. All patients received multiple chemotherapy regimens before autologous BMT. At bone marrow (BM) harvest, only 44% of patients were in complete remission, and overt BM infiltration was present in 37%. After cyclophosphamide and total-body irradiation, no treatment-related deaths were seen. Eleven of the 27 patients relapsed, and four patients developed myelodysplasia/acute myelogenous leukemia. In seven patients in whom pathologic studies were available after relapse, the histology remained DLBCL. Twelve patients remained alive and in complete remission with a median follow-up of 36 months (range 10-132). The disease-free survival and overall survival are estimated to be 46% (90% confidence interval 28-64) and 58% (40-76) at 5 years, respectively. Patients whose disease underwent histologic transformation within 18 months of their initial diagnosis of indolent lymphoma had significantly better overall survival. Selected patients with histologic transformation, particularly those whose transformation occurs early in the course of their disease and who remain chemosensitive, may experience prolonged survival after autoBMT.

Adult↗
PubMed1995

An Effective, Direct Immunomagnetic Procedure for Purging Acute Lymphoblastic Leukemia Cells from Human Bone Marrow.

The AB4 monoclonal antibody, which recognizes an HLA-DR epitope, was found to bind to a high percentage of malignant blast cells in samples obtained from 27 patients with ALL. These included 11 of 11 cases with c-ALL, 3 of 7 with pre-pre-B, and 8 of 9 cases with pre-B ALL. AB4 was used together with anti CD10 and anti CD19 antibodies and super-paramagnetic particles for developing a direct immunomagnetic procedure for purging human bone marrow of leukemic cells. In model experiments with KM3 cells admixed to mononuclear bone marrow cells, the individual antibodies each removed 2.8-3.1 logs and 3.6-4.1 logs of tumor cells with one and two purging cycles, respectively. In comparison, the efficacy of a mixture of the three antibodies was 4.4 logs with one treatment cycle, and > 5 logs with repeated treatments. Whereas the use of a commercially available anti-HLA-DR antibody resulted in a 90% reduction in the survival of CFU-GMs and normal blast colonies, AB4 had only a moderate effect on the progenitor cells (46% and 30% reduction). In conjunction with autologous transplantation, bone marrow from a patient was purged with the antibody mixture and 50% of the CFU-GMs and 47% of the CD34+ cells remained after treatment. The patient showed a normal engraftment, reaching a level of 0.5 x 109/l neutrophils by day 20 and 20 x 109/l platelets by day 30. It is concluded that the antibody cocktail may safely and effectively be used for rapid autograft purging in patients with c-ALL, and also in phenotypically selected cases with other subtypes of ALL.

Journal Article↗
PubMed1997

The role of stem cell transplantation in the treatment of chronic lymphocytic leukemia.

Stem cell transplantation (SCT) is increasingly being used for treatment of chronic lymphocytic leukemia (CLL). The present article summarizes available clinical results and discusses important aspects of SCT in patients with CLL including the preferable type of SCT (allogeneic vs autologous), timing of SCT, high-dose regimens, purging, and molecular monitoring of residual disease.

Bone Marrow Purging↗
PubMed1996

Goralatide (AcSDKP) selectively protects murine hematopoietic progenitors and stem cells against hyperthermic damage.

Hyperthermic purging procedures may be improved by methods that selectively inhibit the proliferative activity of normal hematopoietic progenitors and stem cells, since active proliferation of these subsets is accompanied by increased heat sensitivity. For this reason, bone marrow cells from CBA/H mice were incubated with Goralatide (tetrapeptide Acetyl-N-Ser-Asp-Lys-Pro), a well-known inhibitor of normal hematopoietic progenitor cells to enter the S phase of the cell cycle. Subsequently, the cell suspensions were heat-treated at 43 degrees C for up to 90 minutes. After an exposure of 8 hours to 10(-9) M Goralatide, the number of CFU-GM cells in S phase decreased from 30 to 10%, resulting in an almost 10-fold increase in survival after 90 minutes at 43 degrees C. No effect on the primitive subsets could be detected because of their quiescent cell cycle state in normal bone marrow. To investigate the potential vulnerability of these subsets for Goralatide, bone marrow cells from 5-fluorouracil (5-FU)-pretreated mice were used. 5-FU induced increase in proliferative activity of the CFU-S-12 (day-12 colony-forming units-spleen), and the stem cell with marrow repopulating ability could be abolished by an incubation period with 10(-9) M Goralatide for 16 and 24 hours, respectively. Hence, this decrease in proliferative activity confers a decrease in hyperthermic sensitivity for the primitive hematopoietic subsets. The cytotoxic effect of the incubation on the absolute number of the hematopoietic progenitors and stem cells was <10%. Goralatide treatment (10(-8), 10(-9), and 10(-10) M) up to 24 hours had no effect on the growth kinetics and cell cycle distribution and consequently on the hyperthermic sensitivity of L1210 cells. Based on these results, it can be concluded that Goralatide will have a positive effect on the survival of hematopoietic progenitors and stem cells after hyperthermia and may lead to a gain in the therapeutic window of this purging modality.

Amino Acid Sequence↗
PubMed1991

Assessment of methylprednisolone purging efficacy on Daudi burkitt lymphoma cells from normal bone marrow.

Studies on normal bone marrow and Daudi Burkitt lymphoma cells were performed to determine the efficacy of selective, in vitro chemopurging with methylprednisolone (MP). We found that MP reduces the number of lymphoma cells without significant damage to bone marrow cells. This information is important because we need to improve the existing in vitro purging regimens used to cleanse autologous marrows of metastatic disease before transplantation into cancer patients who have received high-dose chemotherapy. Normal human bone marrow (NBM) and Daudi lymphoma cells were treated in parallel with various purging regimens, NBM death was evaluated using soft-agar culture, while Daudi cell death was evaluated using one-week liquid culture. A protocol of 2.0 mg/mL of MP for four hours demonstrated optimal selectivity. When treatment was followed by cryopreservation, a 1.7 log purge of Daudi cells was increased to 2.3 logs while preserving 36% of committed NBM precursors. We repeated these experiments on a simulated contaminated marrow to model closely the mixture of normal and malignant cells found in advanced, metastatic disease. We evaluated this mixed system by flow cytometric immunoanalysis using the two-color CD10/CD20 markers to detect residual, viable Daudi cells. Our initial results were reproducible in this mixed-cell system, further supporting the evidence for effective in vitro purging of bone marrow using MP.

Bone Marrow Transplantation↗
PubMed2001

[Activation and Cytotoxicity of Bone Marrow Immunocytes by Using Various Cytokines]

The study aimed to explore the changes of the immunocyte quantities and cytotoxicity in bone marrow, and how many hematopoietic progenitor cells retained after the bone marrow cells were activated by different combinations of various cytokines. Bone marrow cells were divided into four groups and were cultured in vitro: (1) Control: no cytokines were added. (2) IL-2 group: bone marrow cells were activated by IL-2. (3) CD3-AK group: bone marrow cells were activated by IL-2 and CD3-McAb. (4) CIK group: IFN-gamma, IL-1, IL-2 and CD3-McAb were added. CFU-GM assay and CD3 phenotype detection were performed before and after activating culture in all groups. The changes of cell quantities during culture and cytotoxicity of cultured cells were tested. CD3 positive cells markedly increased in both CD3-AK and CIK groups. The cell numbers and cytotoxicity of CD3-AK and CIK groups were higher than those of control or IL-2 group obviously after culture (P < 0.05). CFU-GM were decreased in all groups after culture and there had no significant difference among four groups. The combination of IL-2 and CD3-McAb not only stimulates the proliferation of marrow immunocytes and increases their cytotoxicity but retains enough hematopoietic progenitor cells as well. This combination of cytokines can be used to purge autologous bone marrow in vitro.

Journal Article↗
PubMed2001

High-dose therapy and autologous bone marrow transplantation for follicular lymphoma in first complete or partial remission: results of a phase II clinical trial.

Advanced stage follicular small cleaved and mixed cell lymphoma is characterized by relapse from remission and survival ranging from 6 to 12 years. Because young patients have the greatest compromise in longevity, the efficacy and toxicity of high-dose radiochemotherapy and bone marrow transplantation after conventional chemotherapy was evaluated in a prospective phase II clinical trial. Thirty-seven patients in a minimal disease state after conventional chemotherapy received fractionated total body irradiation and high-dose etoposide and cyclophosphamide, followed by purged autologous bone marrow. A reference sample of 188 patients of similar age, stage, and histology managed at this institution before 1988 was identified for comparison of patient characteristics and outcomes. Compared with reference patients, transplant recipients had a higher tumor burden at diagnosis. With a median follow-up of 6.5 years, the estimated 10-year survival after transplantation was 86%. There was a single lymphoma death yielding a 10-year disease-specific survival of 97%. There were 2 early transplant-related deaths and 2 late acute leukemia deaths. Ten patients relapsed, one with microscopic disease only. High tumor burden at diagnosis and incomplete response to chemotherapy adversely influenced survival in the reference but not in the transplanted patients. The estimated risk of death of 14% and relapse of 30% at 10 years in our transplanted follicular lymphoma patients, the majority of whom had high tumor burdens, compares favorably with our observations in appropriately matched reference patients.

Actuarial Analysis↗