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PubMed1996

Factors affecting engraftment and hematopoietic recovery after unpurged autografting in acute leukemia.

Factors affecting hematologic recovery to 0.5 x 10(9)/l neutrophils and 50 x 10(9)/l platelets after unpurged autografting (210 marrow, 30 blood) were analyzed in 240 patients with acute myeloid (AML, n = 128) or lymphoblastic (ALL, n = 112) leukemia. Cytokines were not administered routinely after transplant. Age, sex and cryopreservation did not influence hematologic recovery in multivariate analysis. Blood cell grafts (P < 0.0001), ALL (P = 0.003), and a nucleated cell dose of > or = 2 x 10(8)/kg (P = 0.035) were associated with faster neutrophil recovery. First remission (P = 0.001), a higher cell dose (P = 0.011), ALL (P = 0.023), and a short remission-transplant interval (P = 0.023) were associated with faster platelet recovery. There was a strong correlation between blood cell grafts and higher cell doses, and marrow and lower cell doses. Amongst marrow recipients, neutrophil recovery was faster in ALL (P = 0.001) and with higher cell doses (P = 0.032). Platelet recovery was faster in first remission patients (P = 0.005) and ALL (P = 0.043), and with higher cell doses (P = 0.031). We conclude that hematologic recovery after autografting is faster in ALL and first remission patients, probably due to the nature and the amount of prior chemotherapy. Using blood stem cells hastens engraftment, but even if marrow is used due to concern over relapse with blood, higher cell doses are associated with faster recovery.

Adolescent↗
PubMed1996

Long-term survival in advanced chronic myelogenous leukemia following bone marrow transplantation from haploidentical related donors.

From 1987 to 1991, 26 patients with CML and a median age of 31 years received allogeneic BMT from a partially mismatched related donor (PMRD) who shared at least one haplotype with the recipient. Nine patients were in accelerated phase (AP), and 11 patients were in blast crisis (BC) at the time of BMT. Patients were mismatched either in graft-versus-host or host-versus-graft directions for one antigen in 3 patients, two antigens in 14 patients, and three antigens in 9 patients. All patients were prepared with a regimen consisting of total body irradiation, etoposide, cytosine arabinoside, cyclophosphamide and methylprednisolone. All marrows were treated ex vivo with T10B91.A-31, a monoclonal antibody directed toward the alpha beta heterodimer of the CD3 receptor, and rabbit complement. Additional GVHD prophylaxis included either the anti-CD5 immunoconjugate XomaZyme-H65, cyclosporine, or both in combination with methylprednisolone. Eight patients did not have sustained engraftment. The 100-day survival was 42%. The incidence of > or = grade II acute GVHD was 29%. The incidence of chronic GVHD was 50% and was limited in all cases. The median survival at 4 years for all 26 patients was 27%. Seven patients (CP 1, AP 3, BC 3) remain in hematologic remission 1297-2241+ days after transplantation. AlloBMT from a PMRD may be considered for patients with advanced CML who lack a matched sibling or unrelated donor.

Adolescent↗
PubMed1996

Bone marrow transplantation in chronic GvHD and autoimmune diseases.

The same ex vivo marrow's treatment that we used in mismatched BMT (incubation with vincristine and methylprednisolone) was used in two patients with chronic GVHD and in one patient with PRCA. The conditioning regimen with cyclophosphamide and ALG was aimed to kill only the patient's lymphocytes, and did not cause a deep myeloid aplasia. The patients achieved a clear improvement of their symptoms.

Autoimmune Diseases↗
PubMed1996

Detection of occasional and clonal chromosome aberrations in patients with acute non-lymphocytic leukemia after autologous bone marrow transplantation.

Clonal chromosome aberrations observed in patients who have relapsed after autologous bone marrow transplantation (ABMT) are usually related to the cytogenetic abnormalities observed at diagnosis. In order to assess this relationship, we evaluated 30 acute non-lymphocytic leukemia (ANLL) patients who underwent ABMT at out institution and had evaluable serial cytogenetic studies before and after ABMT. Seventeen patients (57%) showed no chromosome aberrations after ABMT in any of the studies performed, while 13 patients (43%) carried abnormalities. In eight out of 30 patients (27%0 the abnormal karyotype after ABMT was associated with hematologic relapse. The cytogenetic abnormalities were: (1) the same as at diagnosis without additional abnormalities in five patients; (2) the same as at diagnosis but with additional abnormalities in three patients. In one patient a different karyotype from that of diagnosis was detected and a myelodysplastic syndrome was clinically evaluable. Furthermore, occasional and single cell chromosome abnormalities were observed in four patients (13%), none of whom relapsed. The new and additional clonal cytogenetic abnormalities observed after ABMT were found in eight patients (27%), suggesting that this event may not be so frequent, that is presumably associated regimen. The re-appearance of the chromosome aberrations after ABMT and the relationship with the risk of relapse are discussed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Osteogenic growth peptide increases blood and bone marrow cellularity and enhances engraftment of bone marrow transplants in mice.

The osteogenic growth peptide (OGP) was characterized recently in regenerating bone marrow (BM) and normal serum. In vitro, the OGP regulates stromal-cell proliferation and differentiated functions. In vivo, an increase in serum OGP accompanies the osteogenic phase of postablation BM regeneration. The present results in normal mice show that OGP induces a balanced increase in WBC counts and overall BM cellularity. In mice receiving myeloablative irradiation and syngeneic or semiallogeneic BM transplants, OGP stimulates hematopoietic reconstruction and doubles the survival rate; these effects are dependent on initiating the OGP administration before irradiation. Chimerism measurements in semiallogeneic graft recipients suggest no preferential effect of OGP on residual host cells. The data implicate OGP in the acceleration of hematopoiesis secondary to expansion of the stromal microenvironment and/or enhancement of stroma-derived signals to stem cells. The low-dose effectiveness of OGP is explained by the demonstration of an autocrine positive feedback loop that together with the OGP-binding protein sustains high serum levels of the peptide. A potential OGP-based treatment in combination with chemoradiotherapy is attractive because of the OGP-induced balanced multi-lineage enhancement of hematopoiesis and possible replacement of expensive recombinant cytokines by a readily synthesized peptide.

Animals↗
PubMed1997

CD6-depleted allogeneic bone marrow transplantation for acute leukemia in first complete remission.

The appropriate timing of bone marrow transplantation (BMT) for adults with acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) is controversial. Although allogeneic transplantation results in a lower risk of disease recurrence than intensive chemotherapy alone, overall outcome following BMT may not be improved due to the higher incidence of therapy-related fatal complications, frequently as a result of the development of graft-versus-host disease (GVHD). Selective T-cell depletion of donor marrow can reduce the incidence of GVHD and thereby limit transplant-related toxicity. Herein we report the risk of GVHD, incidence of transplant related mortality (TRM), likelihood of disease relapse, and overall survival in adult patients undergoing BMT with CD6 depleted allogeneic marrow for acute leukemia in first remission. Forty-one consecutive allogeneic transplants were performed on patients with acute leukemia and high-risk features (28 AML, 13 ALL) using T12 monoclonal antibody and complement to remove CD6+ T cells from donor marrow. No pre- or posttransplant immune suppressive medications for GVHD prophylaxis were administered. The actuarial estimated risk of grade 2 to 4 acute GVHD was 15% in patients receiving HLA identical grafts. Chronic GVHD developed in five patients. The estimated risk of TRM for patients in first complete remission was 5% at Day +100 and 16% at 2 years. Fatalities attributable to infection with cytomegalovirus or Epstein-Barr virus occurred in only three patients. Estimated probabilities of relapse, overall survival, and event-free survival at 4 years were 25%, 71%, and 63%, respectively. No significant differences in GVHD, TRM, relapse rate, or survival was observed for patients with AML compared with those with ALL. Allogeneic transplantation with CD6 depleted bone marrow is effective in consolidating remissions of high-risk patients with acute leukemia in first remission without excessive toxicity.

Acute Disease↗
PubMedDate not supplied

Allogeneic matched T-cell-depleted bone marrow transplantation for acute leukemia patients.

PURPOSE: We evaluated the efficacy and toxicity of a conditioning regimen designed to overcome the increased risk of rejection and relapse associated with T-cell-depleted bone marrow transplants. PATIENTS AND METHODS: Fifty-four patients with acute leukemia received an allogeneic T-depleted bone marrow transplant from an HLA-matched (n=52) or one locus mismatched (n=2) sibling donor between June 1989 and November 1993. Nineteen acute myeloid leukemia patients and 17 acute lymphoid leukemia patients were in complete remission, and 11 acute myeloid leukemia patients and 7 acute lymphoid leukemia patients were in relapse. Patients were preconditioned with hyperfractionated total body irradiation of 1.2 Gy three times a day on days -9 to -6 (total 14.4 Gy), 10 mg/kg thiotepa on day -5, 4 mg/kg rabbit antithymocyte globulin on days -4 to -1, and 50 mg/kg cyclophosphamide on days -3 and -2. RESULTS: All patients were fully engrafted at a median of 15 days after transplant. No patient rejected the transplant or developed acute or chronic graft-versus-host disease. Of 19 patients with acute myeloid leukemia in complete remission, 14 survive. Four of the 11 patients with acute myeloid leukemia in relapse survive. Twelve acute myeloid leukemia patients died (three of relapse, eight of toxicity, one of other causes). Eleven of 24 patients with acute lymphoid leukemia (one treated in relapse) are alive in complete remission; the other 13 died (nine of relapse, four of toxicity). Interstitial pneumonia, the main cause of toxic death, occurred in 9.26% of total patients. The median follow-up time at this writing is 30 months. CONCLUSIONS: The absence of rejection and graft-versus-host disease and the relatively low relapse and toxicity rates are evidence for the efficacy of our conditioning regimen.

Acute Disease↗
PubMed1997

Supplementation with antioxidants prior to bone marrow transplantation.

Conditioning therapy preceding bone marrow transplantation (BMT) usually consists of high-dose chemotherapy and total body irradiation (TBI). It has acute and delayed toxic effects on several tissues, possibly related to peroxidation processes and exhaustion of antioxidants. Early studies indicated an increase of peroxide processes and a decrease of antioxidants during conditioning therapy. Hence, we investigated the effect of antioxidant supplementation on peroxidation processes and antioxidant status. We supplemented a patient group (N = 16) [BMT (+)], with oral 45 mg beta-carotene, 825 mg alpha-tocopherol and 450 mg ascorbic acid daily for three weeks before conditioning therapy. Another patient group (N = 10), BMT(-), was not supplemented with antioxidants before conditioning therapy. In order to investigate the physiologic effect of supplement antioxidants a healthy control group (N = 10) was supplemented with the same doses as BMT(+). Peroxide concentrations in plasma were measured by using the cholesterol oxidase (CHOD)-iodide method and antioxidants were measured by HPLC. Before supplementation the beta-carotene and alpha-tocopherol concentrations were comparable in both patient groups. After supplementation significantly higher beta-carotene and alpha-tocopherol concentrations were measured in the supplemented patients, BMT(+), than in the unsupplemented patients, BMT(-). After conditioning therapy, BMT(+) patients showed a significantly higher beta-carotene concentration (p < 0.05) than before supplementation. In BMT(-) patients the beta-carotene (p < 0.05) and alpha-tocopherol concentrations (p < 0.01) decreased significantly and the lipid peroxide concentration increased significantly following conditioning therapy. We conclude that antioxidant supplementation prior to conditioning therapy reduces peroxidation processes induced by conditioning therapy in bone marrow recipients.

Adolescent↗
PubMed1997

[Blood selenium content after conditioning and during the course of bone marrow transplantation in children with malignant diseases].

PATIENTS AND RESULTS: Prior to bone marrow transplantation (BMT), at the end of the conditioning phase, we found in 42 investigated children with malignant diseases subnormal lowered plasma- and blood selenium levels. Parallel to the diminished selenium status the plasma glutathione peroxidase activity (Gpx) was not reduced as it is in selenium deficiency, but markedly elevated and probably reflecting cytolytic processes. In the group of combined conditioning (fractionated total body irradiation plus chemotherapy) we found significantly more elevated plasma Gpx values in comparison to the only-chemotherapy group. The renal selenium excretion was elevated during the whole observation and could be caused by disturbed tubular function. CONCLUSION: We conclude, that in the situation of BMT a selenium substitution in a dosage of at least 1 to 2 micrograms Se/kg/d is necessary. Patients' selenium status should be monitored by analyses of plasma- and blood selenium contents.

Adolescent↗
PubMed1994

Our first experience of transfusion support in allogenic bone marrow transplantations.

Incompatibility of blood group antigens in bone marrow transplantation (BMT) requires the depletion of red blood cells from donor bone marrow in order to avoid fatal transfusion reactions. We purified 72 human bone marrows prior to transplantation from red blood cells by a modified method using simple centrifugation and sedimentation in 6% dextran. Small-volume samples (n = 4) were prediluted with compatible homologous red blood cells to reduce the loss of stem cells during the preparation steps. 12 of 30 allogeneic bone marrows were ABO major incompatible with the patient's blood group. Although we did not observe any transfusion reactions nor graft rejections, in ABO incompatible transplantations, donor reticulocytes appeared 10 days later in the peripheral blood than in patients who received an ABO compatible bone marrow. Concordantly, incompatible patients needed 1.7 times more red blood cell units after BMT.

Adolescent↗