Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Bone Marrow Purging”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 361 records · Page 20Linked to original sources

Improved outcome with T-cell-depleted bone marrow transplantation for acute leukemia.

PURPOSE: To eliminate the risk of rejection and lower the risk of relapse after T-cell-depleted bone marrow transplants in acute leukemia patients, we enhanced pretransplant immunosuppression and myeloablation. PATIENTS AND METHODS: Antithymocyte globulin and thiotepa were added to standard total-body irradiation/cyclophosphamide conditioning. Donor bone marrows were depleted ex vivo of T lymphocytes by soybean agglutination and E-rosetting. This approach was tested in 54 consecutive patients with acute leukemia who received transplants from HLA-identical sibling donors or, in two cases, from family donors mismatched at D-DR. No posttransplant immunosuppressive treatment was given as graft-versus-host disease (GVHD) prophylaxis. RESULTS: Neither graft rejection nor GVHD occurred. Transplant-related deaths occurred in six (16.6%) of 36 patients in remission and in seven (38.8%) of 18 patients in relapse at the time of transplantation. The probability of relapse was .12 (95% confidence interval [CI], 0 to .19) for patients with acute myeloid leukemia and .28 (95% CI, .05 to .51) for patients with acute lymphoblastic leukemia who received transplants at the first or second remission. At a median follow-up of 6.9 years (minimum follow-up, 4.9 years), event-free survival for patients who received transplants while in remission was .74 (95% CI, .54 to .93) for acute myeloid leukemia patients and .59 (95% CI, .35 to .82) for acute lymphoblastic leukemia patients. All surviving patients have 100% performance status. CONCLUSION: Adding antithymocyte globulin and thiotepa to the conditioning regimen prevents rejection of extensively T-cell-depleted bone marrow. Even in the complete absence of GVHD, the leukemia relapse rate is not higher than in unmanipulated transplants.

Acute Disease↗

Pain language of bone marrow transplantation patients.

Previous studies have shown that hypnosis may be effective in reducing intensity of pain among bone marrow transplantation patients whereas cognitive behavioral intervention without imagery was not effective for this group of patients. Since hypnosis alters patients' perception of pain and cognitive behavioral intervention changes patients' beliefs and improves their coping with pain, we hypothesized that sensory pain is more important than affective pain in understanding the pain experience of patients undergoing bone marrow transplantation. To test this hypothesis we administered the McGill Pain Questionnaire longitudinally to 50 consecutive eligible recipients of bone marrow transplantation during hospitalization to assess the different dimensions of pain they experienced. Consistent with our hypothesis, sensory pain fluctuated with treatment stages, and the pattern was consistent with previous findings. Patients reported significantly higher sensory pain than affective pain at all assessment points. In contrast, affective pain remained low and stable throughout the treatment. Our results contribute to the understanding of the nature of pain in bone marrow transplantation and suggest pain management strategies that focus on sensory pain as in hypnosis are more useful for such patients.

Adaptation, Psychological↗

Use of recombinant human interleukin-2 in conjunction with bone marrow transplantation as a model for control of minimal residual disease in malignant hematological disorders: I. Treatment of murine leukemia in conjunction with allogeneic bone marrow transplantation and IL-2-activated cell-mediated immunotherapy.

Immunotherapy with recombinant human interleukin-2 (IL-2) and allogeneic spleen cells has led to significant antitumor effects in B-cell leukemia- (BCL1) bearing mice following transplantation with T-lymphocyte-depleted allogeneic bone marrow cells. Graft versus leukemia (GVL) effects were studied in a model mimicking minimal residual disease following bone marrow transplantation (BMT). Lethally irradiated (BALB/c x C57BL/6)F1 recipients were reconstituted with 20 x 10(6) T-lymphocyte-depleted C57BL/6 bone marrow cells mixed with 10(4) to 10(6) BCL1 cells followed by administration of sequential increments of allogeneic C57BL/6 spleen cells; 10(6) cells on Day +1, 10(7) cells on Day +5, and 5 x 10(7) cells on Day +9, with or without concomitant IL-2 treatment (intraperitoneal injections of 20,000 U twice daily for 3 days) together with each spleen cell administration. All mice receiving 10(4)-10(6) BCL1 cells developed marked splenomegaly by Day +21 and all adoptive recipients of 10(5) spleen cells obtained from these mice developed leukemia within 21-36 days. Treatment of mice which received 10(4) BCL1 cells by either three courses of low dose IL-2 or three increments of allogeneic spleen cells alone and certainly by a combination of both resulted in normalization of splenomegaly on Day +21, but only adoptive recipients of 10(5) spleen cells obtained from mice treated by both allogeneic spleen cells and IL-2 (10/10) or allogeneic spleen cells alone (8/10) were disease free (greater than 100 days). Mice inoculated with 10(5) BCL1 cells developed mild splenomegaly on Day +21 after IL2 treatment alone, but showed no clinical evidence of disease following administration of allogeneic spleen cells or both allogeneic spleen cells and IL-2. Following adoptive transfer of 10(5) spleen cells obtained from each treated group no leukemia (greater than 100 days) was evident in recipients of spleen cells obtained from mice treated with both allogeneic spleen cells and IL-2 (10/10) whereas a partial effect was observed in mice treated by allogeneic spleen cells only (4/10). Mice inoculated with a high dose of BCL1 cells (10(6] showed some delay in onset of splenomegaly, but no curative antileukemic effects could be observed even following a synergistic combination of IL-2 and allogeneic spleen cells. Our data suggest that immunocompetent allogeneic lymphocytes may play an important role against leukemic relapse and thus cell therapy may be used therapeutically to treat minimal residual disease after BMT even following initial reconstitution with T-cell-depleted bone marrow cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Comparison of the survivals between bone marrow transplantation and chemotherapy for acute leukemia in first remission--a Japanese single institution study.

The outcome of sixty-four patients with acute leukemia in first remission who had been treated with either bone marrow transplantation (BMT) or conventional chemotherapy was retrospectively evaluated (a median follow-up of 37 months). Among them, 26 patients (age range; 14-42 years) received allogeneic BMT from HLA-identical siblings and 38 patients (age range; 13-43 years) who had no HLA-identical donors undertook the continued combination chemotherapy. Kaplan-Meier product-limit estimate of actuarial survival of acute myelogenous leukemia (AML) patients was 48.9% for the BMT group and 15.7% for the chemotherapy group (p = not significant, NS). For acute lymphoblastic leukemia (ALL) patients, the survival following BMT was 80.2% and was significantly higher than that of the chemotherapy group of 33.3% (p < 0.05). The disease-free survival of AML and ALL for the BMT group was 34.3% and 36.5%, respectively, which was higher than that of the chemotherapy group (16.7% and 23.4%, respectively (p = NS)). These findings in our Japanese single institution study suggested that BMT may be the treatment of choice for adult patients with acute leukemia in first remission if they had suitable donors and that more effective therapeutic regimens were necessary for patients without compatible donors in order to obtain the longer remission duration.

Acute Disease↗

The current position of allogeneic and autologous BMT in multiple myeloma.

The projected outcome of allogeneic BMT for myeloma based on the EBMT data is as follows: for patients transplanted after first line therapy there is a 30% risk of transplant related death, a 55% chance of being alive at 5 years and a 35% chance of being alive in complete remission at 5 years. If BMT is performed later in the course of the disease, the risk of transplant related death is increased and the chance of long term relapse-free survival correspondingly reduced. Conversely, ABMT has a low mortality risk, but there is currently no evidence that ABMT using unpurged marrow can produce long term cure as no series has shown any evidence of a plateau in remission duration. The early results of maintenance interferon are encouraging but longer follow-up is needed to determine whether the proportion of patients in continuing remission at 5 years will approach that seen after allogeneic BMT. Early results of peripheral blood stem cell transplantation are also encouraging but longer follow-up is required. It remains extremely important when comparing results of ABMT with chemotherapy alone to compare similar patient groups, bearing in mind that patients who have autologous transplantation in first response are by definition responders with good performance status and without significant renal failure. In order to address this problem in a prospective manner, a randomised study has been planned by the EORTC in collaboration with the EBMT. In this study, patients with adequate renal function will be randomised at diagnosis to chemotherapy followed by either autologous BMT or continuing chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Marrow Purging↗

Busulfan and cyclophosphamide versus cyclophosphamide and total body irradiation for marrow transplantation in chronic myelogenous leukemia--a review.

Allogeneic bone marrow transplantation (BMT) for chronic myelogenous leukemia (CML) offers the only significant chance of cure for this disease. About 50% of patients transplanted in the 1980s appear to be cured and with subsequent advances, it is suggested that more patients transplanted in the 1990s will be cured. Cyclophosphamide (Cy) (120 mg/kg) followed by fractionated total body irradiation (TBI) (Cy2/TBI) has been usually employed in preparation for BMT. Alternative regimens of Busulfan (Bu) (16 mg/kg) and Cy (120 mg/kg) (Bu/Cy2) or Bu (16 mg/kg) and Cy (200 mg/kg) (Bu/Cy4) have more recently been employed. At least three studies of Bu/Cy2 or Bu/Cy4 have given encouraging results. Two ongoing randomized studies of Bu/Cy2 versus Cy2/TBI have shown no difference in the event free survival (EFS). In addition, two ongoing randomized studies of Bu/Cy4 versus Cy (200 mg/kg) plus TBI (Cy4/TBI) show no significant differences in EFS. It appears that Bu/Cy regimens are as effective as Cy/TBI regimens. The choice of one regimen over the other depends on matters other than therapeutic efficacy.

Adolescent↗

Is there any future for T-cell depleted bone marrow transplantation in chronic myeloid leukaemia?

There is no doubt that the poor reputation of T-cell depleted bone marrow transplant arises from its use in CML patients, where an increase in graft rejection and, above all, in leukaemia relapse has been reported by almost all centres. Evidence suggests that the standard conditioning regimen (once thought to be sufficiently immunosuppressive and myeloablative in unmanipulated transplants) should no longer be considered adequate when the immunological balance has shifted in favour of unopposed host-versus-graft reactivity and the GvL effect is lacking. Since GvHD remains the major problem in BMT, we suggest T-cell depletion should be considered the most effective method for GvHD prophylaxis but the cytoreductive effect of the conditioning regimens and the anti-leukaemia immune reactivity should be enhanced.

Adolescent↗

Clinical models of autotransplants in chronic myelogenous leukemia.

We analysed relapse risk after syngeneic and allogeneic T cell depleted transplants to predict the outcome after autotransplants in chronic myelogenous leukemia (CML). These data suggest that high dose pre-transplant conditioning may cure about 50% of the persons in chronic phase and about 10% of those in more advanced phases. The expected relapse rate would be about 50-90%. However, additional relapses might occur from infusing leukemia cells with the graft. Different approaches are being attempted to eliminate leukemia cells from the graft. It is however unlikely that their effect could be demonstrated in clinical trials. Recent analyses in persons relapsing after allogeneic T depleted transplants suggest that reducing the CML cell mass by high dose chemotherapy may prolong duration of survival.

Antineoplastic Combined Chemotherapy Protocols↗

Karyotypic conversion by interferon as preparative treatment for autologous BMT in Ph positive CML. Italian Cooperative Study Group (ICSG) on Chronic Myeloid Leukemia.

This is an interim report of the Roferon A/ABMT protocol by ICSG on CML aimed at investigating the feasibility and potential of combining treatment with alpha-IFN with ABMT in Ph+ CML. Of 675 Ph+ CML patients recruited between January 1989 and January 1991 by 44 Italian institutions, 398 were 55 or less years old and eligible for the protocol. Of 132 patients who completed IFN treatment 118 had evaluable karyotype; of these only 48 showed > 25% Ph--metaphases and were eligible for BM harvest. In 24 patients BM was collected and 13 were submitted to ABMT. The major causes of drop out from the protocol were shift to allogeneic BMT, accelerated blastic phase, patient refusal and logistic problems. Data on hematologic reconstitution are presently available in 11 patients: Neutrophils were > 0.5 x 10(9)/l in 23 days (median), (range 16-40 days); platelets reached 50 x 10(9)/l in 28 days (median), (range 25-100 days). One patient had a very delayed BM take and was rescued with autologous peripheral blood stem cells collected at diagnosis.

Adult↗

Management of chronic myeloid leukemia in chronic phase with autologous stem cell transplantation and alpha-2 interferon: cytogenetic and clinical results.

Forty-eight patients with chronic myeloid leukemia (CML) in chronic phase (CP) were treated by autologous stem cells transplantation (ASCT) and alpha Interferon (IFN) with three approaches: 1) ASCT at diagnosis followed by IFN, 2) ASCT post IFN with cells collected after an interval from IFN discontinuance, followed by IFN, 3) ASCT in patients selected by cytoconversion obtained with IFN, performed soon after IFN discontinuance. Following ASCT, a major karyotype response (more than 65% Ph1 negative cells, MKR) was observed at least once in 40%, 53% and 83% of patients from the three groups, respectively. At last follow-ups (median 39, 40 and 21 months, respectively) 19%, 13% and 67% of patients still present a MKR with 2 patients from group 1 and 4 patients from group 3 being 100% Ph' negative. Projected survival from diagnosis is 77% at 52 months for patients from group 1 and 47% at 75 months for patients from group 2. Present data indicate that 1) IFN can stabilize results obtained with ASCT, 2) ASCT can potentiate responses to IFN, 3) combined ASCT and IFN can improve survival. Longer follow-up of patients and randomized studies are required to define the real impact on disease outcome by these treatment approaches.

Adult↗

Intensive sequential therapy for VAD-resistant multiple myeloma.

Few effective regimens are available for patients with advanced multiple myeloma resistant to alkylating agents and VAD. We treated 65 patients with advanced and refractory multiple myeloma with the combination of cyclophosphamide (3.0 gm/m2) and etoposide (900 mg/m2) followed by GM-CSF at a daily dose of 0.125 mg/m2. Thirty-five percent of patients responded with a 6% mortality rate. After a median of 2 months, 16 patients received myeloablative treatment supported by autologous bone marrow or blood stem cells. Four of ten previously resistant patients responded so that the overall response rate was 42%. The median survival for all patients was 10 months and the median remission was 8 months. The median survival for patients with both low serum lactate dehydrogenase and B2 microglobulin, or for those who received myeloablative treatment, was projected at 18 months. Our combination of cyclophosphamide and etoposide provided an effective rescue treatment for many patients with advanced multiple myeloma resistant to conventional therapies. This program allowed early blood stem cell collection in support of subsequent myeloablative therapy for selected patients.

Adult↗