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PubMed1994

Impairment of nasal mucociliary clearance during bone marrow transplantation. University of Nebraska Medical Center bone Marrow Transplantation Pulmonary Study Group.

Transient mucositis occurs in almost all patients receiving bone marrow transplantation (BMT) but it is not known whether airway mucociliary transport is impaired during this period. We hypothesized that the preparative regimen associated with BMT impairs mucociliary clearance during the peri-transplant period. To test this hypothesis we determined nasal saccharine transit time (STT) and a mucositis score daily throughout the peri-transplant hospitalization in 13 patients receiving BMT. STT was prolonged in all patients at some time during the peri-transplant period and mucociliary clearance was ineffective in 12 of 13 patients for an average of 22% of the days. STT was most prolonged (about 155% of baseline) in the 2 week period following marrow infusion and correlated with the appearance of mucositis. STT returned to baseline values within 30 days after marrow infusion in all but one patient. These findings demonstrate that nasal mucociliary clearance is significantly impaired in most patients during BMT, if only temporarily. This decrease in local airway host defense may explain, in part, the increased risk of upper respiratory infections that these patients experience.

Adult↗
PubMed1989

Effect of methotrexate on relapse after bone-marrow transplantation for acute lymphoblastic leukaemia. International Bone Marrow Transplant Registry.

Data from 634 patients who received HLA-identical bone-marrow transplants for acute lymphoblastic leukaemia in first or second remission were analysed to examine the influence of mode of prophylaxis against graft versus host disease on rate of relapse of leukaemia. Methotrexate was associated with a significantly lower risk of leukaemia recurrence than were other methods of GVHD prophylaxis (relative risk 0.2, p less than 0.0003, for first-remission transplants; relative risk 0.3, p less than 0.0001, for second remission transplants). The decreased risk of relapse did not seem to be mediated via an impact on incidence or severity of graft versus host disease. A direct antileukaemia effect of methotrexate is the most likely mechanism.

Actuarial Analysis↗
PubMed1997

Massive bone marrow necrosis as the presenting feature in a case of primary bone marrow high grade non-Hodgkin's lymphoma.

Massive bone marrow necrosis (MBMN) is a rare complication of non-Hodgkin's lymphoma (NHL) and usually occurs in the late stage of the disease. Primary bone marrow NHL with no evidence of disease elsewhere in the lymphoreticular system is also rare. Here a case of primary bone marrow high grade NHL is reported who presented with MBMN without any evidence of nodal or other extra-nodal disease.

Adult↗
PubMed1993

1993 progress report from the International Bone Marrow Transplant Registry. Advisory Committee of the International Bone Marrow Transplant Registry.

The International Bone Marrow Transplant Registry is an organization devoted to scientific research in BMT. More than 230 transplant teams worldwide contribute detailed information about recipients of allogeneic and syngeneic BMT for study. Results of analyses are published in medical journals and presented at national and international scientific meetings (more than 60 publications and more than 500 presentations in the past 4 years). This collaborative research program has grown rapidly with more than 2000 cases reported annually. This report summarizes results of several recent investigations and reviews the state of BMT in leukemia and aplastic anemia.

Anemia, Aplastic↗
PubMed1996

Myeloablative therapy and bone marrow rescue in advanced neuroblastoma. Report from the Italian Bone Marrow Transplant Registry. Italian Association of Pediatric Hematology-Oncology, BMT Group.

This study reports a large cooperative experience in myeloablative therapy and bone marrow rescue undertaken to define better the outcome of children with disseminated neuroblastoma after megatherapy. Between 1984 and 1993, 135 children underwent myeloablative therapy with bone marrow transplantation (BMT) in nine Italian Centres. One hundred and seventeen children received unpurged autologous BMT, five allogeneic BMT and 13 peripheral blood progenitor cells as rescue. Of these 135 children, 57 were in 1st CR, 11 in 2nd or subsequent CR, 42 in 1st PR, and 25 had more advanced disease. Twelve children (9%) died of toxicity, 86 relapsed or progressed at 1-68 months (median 7 months) and 80 of these subsequently died of progressive disease. Forty-three children are still alive with 37 in continuous remission at a median of 65 months (30-123 months) after BMT. Overall and disease-free survival at 8 years are 28.5% (s.e. 4.3) and 26% (s.e. 4), respectively. Disease-free survival is 34.6% (s.e. 6.7) for the patients grafted in 1st complete remission, 23.6% (s.e. 6.6) for patients grafted in 1st partial remission, 36.4% (s.e. 14.5) for patients grafted in 2nd or subsequent CR, and 8% (5.4) for patients with advanced disease. We conclude these data confirm that early toxicity of myeloablative therapy is manageable and that myeloablative therapy with bone marrow rescue may contribute to an improved long-term survival of children with disseminated neuroblastoma but the objective of cure of all patients remains distant.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Mouse skin graft prolongation with donor strain bone marrow and anti-lymphocyte serum: surface markers of the active bone marrow cells.

The survival of C3H/HeJ skin grafts on B6AF1 mice treated with anti-lymphocyte serum (ALS) can be significantly prolonged by the injection of the host with C3H/HeJ bone marrow. Although the prolongation is apparently due at least in part to the ultimate presence in the host of specific suppressor cells of donor origin, little is known about the nature of the cells in the marrow inoculum that are responsible for this effect. The present investigation was undertaken to characterize surface markers of the active bone marrow cells. Marker-positive populations were either depleted and enriched by panning techniques or depleted by killing with specific antibody and complement, and then were assayed for their ability to prolong graft survival. Cells that were adherent to anti-Ia-coated plates extended graft survival only slightly better than did treatment with ALS alone, whereas nonadherent (Ia-depleted) cells, as well as cells treated with anti Ia and complement, retained good prolonging activity. Similarly, panning on anti-immunoglobulin (Ig)-coated plates produced an active, Ig+-depleted population and an inactive adherent population, and killing of Thy-1+ cells with antibody and complement did not compromise the ability of the bone marrow inoculum to prolong graft survival. Complement receptor-positive (EAC+) and Fc gamma receptor-positive cells (EA+) were separated by panning on plates coated with sheep erythrocytes/antibody/complement and erythrocytes/7S antibody respectively. Adherent, EAC+-enriched cells were only slightly active, whereas the nonadherent, EAC-depleted population was fully active in graft prolongation. However, both Fc gamma R+ (EA+)-enriched and depleted populations were active, with the enriched fraction producing significantly better prolongation than the depleted population. Thus, the bone marrow cells that can prolong skin graft survival in ALS-treated mice appear to be Ia-, Thy-1+, largely complement receptor negative, and Ig-, but are largely positive for Fc gamma receptors.

Animals↗
PubMed1993

[Bone marrow transplantation with major ABO incompatibility. Experience at the bone marrow transplantation unit of the Center of Lisbon at the IPOFG].

Thirteen patients submitted to major ABO incompatible, HLA A and B identical, mixed lymphocyte culture negative bone marrow transplantation (BMT) were retrospectively evaluated. Gravity sedimentation by hydroxyethyl starch was used in almost all cases to deplete erythrocytes from bone marrow (12/13): a removal rate or 90%--corresponding to an erythrocyte residual volume of 27.4 rate ml--and a nucleated cell recovery of 76% (mean values) were obtained. All patients underwent a hyperhydration regimen and received corticosteroid prophylaxis before bone marrow infusion. Considering the most important immunohematological problems associated to this type of transplant we verified that seven patients developed minor complications, and among them only one had long term consequences. In comparison with the control group, ABO identical and with minor incompatibility, the study group had delayed onset of erythropoiesis and needed greater erythrocyte transfusion support. We concluded that major ABO incompatibility does not constitute a drawback to BMT success in most patients.

ABO Blood-Group System↗
PubMed1999

Application of interphase FISH on direct bone marrow smears for evidence of chimerism in pediatric sex mismatched bone marrow transplantation.

We report here our experience in the management of four children undergoing sex mismatched allogeneic bone marrow transplantation (BMT) who showed evidence of poor engraftment post BMT. Fluorescence in situ hybridisation (FISH) was performed on direct bone marrow smears with the X centromere and Y heterochromatin probes, to ascertain chimerism. Of 16 hybridisations, only one was unsuccessful, whereas routine bone marrow cytogenetics performed at the same time failed in five of eight cultures. The FISH results were available in one to two days. The FISH findings provided a valuable aid in the early management of these children.

Bone Marrow Examination↗
PubMed1982

Pretreatment of donor bone marrow with monoclonal antibody OKT3 for prevention of acute graft-versus-host disease in allogeneic histocompatible bone-marrow transplantation.

Ten consecutive patients undergoing transplantation of bone marrow from histocompatible siblings for treatment of haematological malignancy took part in a pilot study to test the safety of in-vitro treatment of donor bone marrow with monoclonal antibody OKT3. Three male and seven female patients aged 7-34 years received concentrated bone marrow buffy-coat cells which had been incubated with OKT3 before infusion. In-vitro studies confirmed that almost all immunocompetent T lymphocytes in the bone-marrow samples were coated with OKT3 at the time of infusion. In vitro, neonatal rabbit complement inhibited the proliferation of bone-marrow T lymphocytes in samples preincubated with OKT3 to less than 4% of the mitogenic responses of the untreated bone marrow. In contrast, fresh autologous complement did not effectively lyse OKT3-treated bone-marrow cells. Infusion of OKT3-treated bone marrow was safely accomplished, and engraftment was achieved in all patients (mean 23 days). Nine of ten patients survived for more than 100 days after bone-marrow transplantation, but significant acute graft-versus-host disease (GvHD) requiring treatment with steroids developed in five of the ten. This finding suggests that further modifications for bone-marrow pretreatment will be needed to achieve effective prophylaxis against acute GvHD in histocompatible bone-marrow transplantation.

Acute Disease↗
PubMed1989

A comparison between regimens containing chemotherapy alone (busulfan and cyclophosphamide) and chemotherapy (V. RAPID) plus total body irradiation on marrow engraftment following allogeneic bone marrow transplantation.

The effect of two conditioning regimens given prior to allogeneic bone marrow transplantation (BMT) on the kinetics of engraftment were compared. 5 patients received busulfan and cyclophosphamide: 7 patients received daunorubicin, vincristine, cytosine arabinoside, methylprednisone and VM-26 plus total body irradiation (TBI). Bone marrow progenitors (BFU-E, CFU-E, CFU-GM, CFU-F) were assayed up to 3 months post-BMT. All progenitors were severely depressed in spite of peripheral blood recovery. There was no stromal recovery in any adult patient post-BMT. There was no significant difference in time to engraftment, or colony forming units, or between patients conditioned with chemotherapy alone or chemotherapy plus TBI. We were unable to detect effects of graft-versus-host disease or cytomegalic viral infection on bone marrow progenitors or peripheral blood recovery in this study.

Bone Marrow↗
PubMed1997

Quality of life measurement in bone marrow transplantation: development of the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) scale.

We developed a 12-item bone marrow transplant subscale (BMTS) for the general Functional Assessment of Cancer Therapy (FACT) measure. The subscale combined with the FACT, (FACT-BMT) is a 47-item, valid and reliable measure of five dimensions of quality of life in bone marrow transplant patients. The three-step validation process involved the generation and selection of BMT-specific items and the testing of the overall measure. Items were selected from a list produced by seven oncology experts and 15 patients and were designed to assess content not represented in the general FACT items. A total of 182 patients completed the FACT-BMT at baseline, prior to BMT. An analysis measuring sensitivity to change was performed with 74 patients after transplantation and 60 patients over the three time-points of baseline, hospital discharge and 100 days. The FACT-BMT and all subscales were correlated, sensitivity to change was measured, and the internal consistency for each scale was calculated. Coefficients of reliability and validity ranged from 0.86 to 0.89 for the entire FACT-BMT and 0.54 to 0.63 for the BMTS. The BMTS was able to discriminate patients on the basis of performance status rating and also demonstrated sensitivity to change over time. The FACT-BMT has good psychometric properties for use in assessing quality of life in bone marrow transplant patients. The addition of the bone marrow transplant subscale to the general FACT measure makes it an excellent choice for use in BMT clinical trials.

Adolescent↗
PubMed2004

The use of bone marrow stem cells for bone tissue engineering.

Bone marrow stem cells (BMSC), known for its multipotency to differentiate into various mesenchymal cells such as chodrocyte, osteoblasts, adipocytes, etc, have been actively applied in tissue engineering. BMSC have been successfully isolated from bone marrow aspirate and bone marrow scraping from patients of various ages (13-56 years) with as little as 2ml to 5ml aspirate. BMSC isolated from our laboratory showed the presence of a heterogenous population that showed varying prevalence of surface antigens and the presence of telomerase activity albeit weak. Upon osteogenic induction, alkaline phosphatase activity and mineralization activity were observed.

Bone Marrow Cells↗
PubMed1993

Immunoglobulin gene rearrangement in plasma cell dyscrasias: detection of small clonal cell populations in peripheral blood and bone marrow.

The bone marrow (BM) and peripheral blood (PB) samples of 71 patients with plasma cell dyscrasias were analysed by the Southern blot technique for the presence of clonal immunoglobulin (Ig) gene rearrangements. 53% of BM samples examined were archival material such as air dried BM slides or frozen trephine biopsies. The results were related to bone marrow plasmacytosis as determined by cytology and flow cytometry, and other clinical parameters. Clonal Ig gene rearrangements were found in BM samples of 45 (83%) of 54 MM patients and in 3 of 6 patients with monoclonal gammopathy of unknown significance (MGUS). Clonal cell populations in the PB were detected in 11 (30%) of 37 examined MM patients, but in none of the patients with MGUS or solitary plasmacytoma of bone. PB involvement was associated with progressive disease. Circulating monoclonal cells were significantly associated with higher M-protein levels (p < 0.05). Thus, circulating clonal precursor cells are encountered more frequently in active MM.

Adult↗