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PubMed1989

Assessment and management of donor pain following marrow harvest for allogeneic bone marrow transplantation.

We studied the time course and intensity of pain of multiple bone marrow aspirations in 30 healthy adult marrow donors receiving acetaminophen with codeine for analgesia immediately after marrow harvesting for allogeneic bone marrow transplantation. Upon discharge, donors were supplied with acetaminophen (315 mg) plus codeine (30 mg) tablets and instructed to use one or two tablets up to every 4 h as needed for pain control. Donors used analgesic medication for a mean (+/- SE) of 3.3 +/- 0.5 days (range = 1-13 days) and reported less than complete pain relief. Subjects reported more pain at time of medication than between doses, indicating that the analgesic was at least partially effective. Male donors tended to report more pain and use more analgesic than did females. We conclude that donors self-regulate their analgesic usage to achieve maximal relief and that incomplete relief with acetaminophen plus codeine may be due to limited efficacy of this analgesic preparation. Our findings suggest that donor pain management may be improved by use of more powerful analgesics.

Acetaminophen↗
PubMed2003

Enhancement of spine fusion using combined gene therapy and tissue engineering BMP-7-expressing bone marrow cells and allograft bone.

STUDY DESIGN: Prospective study to assess the enhancement of spine fusion using a tissue engineering construct consisting of bone marrow cells genetically modified by adenovirus (Ad) vector-encoding bone morphogenetic protein-7 (BMP-7) seeded onto an allograft scaffold in a rat model. OBJECTIVES: To evaluate Ad transgene expression at the fusion site and the effect of AdBMP-7-treatment on fusion rates, mechanical stability, microscopic anatomy, and bone formation rates. SUMMARY OF BACKGROUND DATA: Nonunion is a major complication of spine fusion. Gene transfer may be an effective method for locally overexpressing BMP-7, a gene important for bone formation and regeneration to enhance allograft spine fusion. MATERIALS AND METHODS: Bone marrow cells were treated with AdBMP-7 or Adbetagal (encoding the marker gene beta-galactosidase), AdNull (with no gene), or no vector and implanted with allograft in a site of posterior spine fusion. Marker gene expression was assessed up to 14 days after administration. Fusions were evaluated at 8 weeks. RESULTS: Ad gene expression was maximal on day 3, waning to background levels by 14 days. With AdBMP-7 treatment, radiographic fusion rate was 70% and mechanical fusion rate was 80% versus 0% by either parameter in control groups. Fused AdBMP-7-treated spines had a 2.5-fold to 3.0-fold lower range of motion and 1.7-fold to 1.9-fold lower hysteresis than controls. Fusion masses of AdBMP-7-treated spines had the microscopic appearance of normal trabecular bone and showed a 23-fold higher uptake of fluorochrome indicating increased bone formation. CONCLUSIONS: Addition of AdBMP-7-modified marrow cells can enhance allograft spine fusion.

Adenoviridae↗
PubMed1992

Rapid and automated processing of bone marrow grafts without Ficoll density gradient for transplantation of cryopreserved autologous or ABO-incompatible allogeneic bone marrow.

The growing number of BMTs has increased interest in safe and standardized in vitro bone marrow processing techniques. We describe our experience with a rapid automated method for the isolation of mononuclear cells (MNC) from large volumes of bone marrow using a Fenwal CS-3000 cell separator without employing density gradient materials. Forty bone marrow harvests with a mean volume of 1650 +/- 307 ml were processed. A mean of 75 +/- 34% (50 percentile range 54-94%) of the original MNCs were recovered in a volume of 200 ml with only 4 +/- 2% of the starting red blood cells (RBC). Removal of granulocytes, immature myeloid precursors and platelets proved to be sufficient to permit safe cryopreservation and successful autologous BMT (n = 25). Allogeneic BMT (n = 14, including three major ABO-incompatible) could be performed without additional manipulation. In both groups of patients timely and stable engraftment comparable to historical controls receiving Ficoll gradient processed autologous (n = 17) or unprocessed allogeneic BMT (n = 54) was observed. Moreover, 70 +/- 14% of the RBC could be recovered from the grafts. They were used for autologous RBC support of donors, rendering unnecessary autologous blood pre-donations.

ABO Blood-Group System↗
PubMed2003

[Evaluation of bone marrow involvement by FDG-PET for refractory Hodgkin lymphoma treated by unrelated allogeneic bone marrow transplantation].

A 23-year-old female patient was diagnosed as having Hodgkin lymphoma (mixed cellularity type, clinical stage III B) in September 2000. She underwent ABVD chemotherapy and irradiation of a mediastinal lesion, resulting in complete remission. However, the disease reoccurred three month after the completion of initial treatment. She was admitted to our hospital for allogeneic stem cell transplantation. Thoractic vertebra, lumbar vertebra and iliac bone lesions were detected by FDG-PET, and a diagnosis of bone marrow infiltration was made. She received re-induction chemotherapy but did not achieve complete remission. A residual lesion in her bone marrow was detected by FDG-PET. She underwent unrelated allogeneic bone marrow transplantation in May 2002. Preconditioning was VP-16, CY and TBI. Engraftment of white blood cells was on day 15. Skin GVHD was detected at the same time and she was treated with steroid hormones, resulting in improvement. No residual mass could be detected by FDG-PET on day 60. However, she suffered from fever on day 80. Aggravation of the disease was revealed and she died from progression of the disease on day 120. FDG-PET is useful for the monitoring disease status and for determining the optimal timing of various treatments.

Adult↗
PubMed1996

Bone marrow collected 14 days after in vivo administration of granulocyte colony-stimulating factor and stem cell factor to mice has 10-fold more repopulating ability than untreated bone marrow.

We have examined the repopulating ability of bone marrow and peripheral blood cells collected immediately and at intervals after treatment of donor mice with the combination of granulocyte colony-stimulating factor (G-CSF) and stem cell factor (SCF). Using a competitive repopulation assay we showed that the repopulating ability of peripheral blood cells was highest immediately after cytokine treatment and declined to normal levels within 6 weeks of the termination of treatment with G-CSF and SCF. In contrast the repopulating ability of bone marrow cells was low immediately after cytokine treatment and increased to levels that were 10-fold or more greater than marrow from untreated mice by 14 days after termination of treatment with G-CSF and SCF. This high level of repopulating activity declined to normal levels by 6 weeks after termination of treatment with G-CSF and SCF. The high level of repopulating ability was confirmed by injecting cells from G-CSF- and SCF-treated donors into unconditioned recipients. Peripheral blood cells collected immediately after treatment with G-CSF and SCF engrafted into unconditioned mice sevenfold better than an equivalent number of bone marrow cells from untreated mice. Likewise, bone marrow cells collected 14 days after treatment of the donor animal with G-CSF and SCF engrafted at 10-fold higher levels than an equivalent number of bone marrow cells from untreated mice. We conclude that the treatment of donor mice with G-CSF and SCF causes a transient increase in the repopulating ability of peripheral blood and later of bone marrow. These observations may have applications to clinical hematopoietic stem cell transplantation.

Animals↗
PubMed1993

HIV infection in autologous and allogeneic bone marrow transplant patients: a retrospective analysis of the Marseille bone marrow transplant population.

Twelve HIV-positive patients who either underwent or seroconverted after bone marrow transplantation (BMT) at the University of Marseille between 1981 and 1985 were reviewed in order to observe their rates of development of AIDS. Two patients were HIV positive prior to transplantation, while ten seroconverted after transplantation. Six patients underwent autologous BMT and six underwent allogeneic BMT; all of their respective donors were seronegative. Eleven patients developed AIDS (92%), with a mean AIDS-free time (AFT) of 1 year 8 months after BMT. Seven of those subjects died, with a mean survival over a 5-year follow-up period of 2.14 years after BMT. Five autologous recipients had a mean AFT of 2 years 3 months, with the sixth patient being AIDS free. The mean AFT for the allogeneic recipients was 1 year 2 months (p = NS), all of whom developed AIDS. These data suggest that the development of AIDS was rapid from the time when our patients seroconverted. However, this was not initially accompanied by poor survival. In summary, BMT may be indicated for HIV-positive patients who required myeloablation, despite an enhanced development of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1992

[Studies of human bone marrow stromal cells--effects of antimetabolites on the growing dynamics of human bone marrow cells and their support of hemopoietic cells].

The effects of antimetabolites on the growing dynamics of human bone marrow stromal cells and their support of hemopoietic cells were tested by using a modified version of Dexter's culture system. Cytosine arabinoside (ara-C) was found to suppress neither the growing dynamics nor the supportability. On the other hand, methotrexate (MTX) suppressed the supportiveness, even though it hardly suppressed the growing dynamics. The recognition of injury to marrow cells could be of potential importance in cancer chemotherapy. Our in vitro evidence may provide clinical insights for cancer chemotherapy including prolonged marrow suppression or pretreatment of bone marrow transplantation.

Adult↗
PubMed1994

Autologous bone marrow transplantation for pediatric Wilms' tumor: the experience of the European Bone Marrow Transplantation Solid Tumor Registry.

This survey includes 25 children with Wilms' tumor undergoing high-dose chemotherapy associated with autologous bone marrow transplantation (ABMT) in the period June 1984-December 1991 and enrolled in the European Bone Marrow Transplantation Registry for Solid Tumors. At diagnosis, 12 children presented stage IV disease, 5 stage III, 3 stage II, and 5 stage I. Before ABMT, 21 children had 1 to 4 relapses (median 1); 13 achieved a second or subsequent complete remission (CR), four stage IV children failed to respond to first line treatment and achieved either CR (3 patients), or partial remission (PR) after second line therapy. At high-dose chemotherapy, 17 children were in CR and 8 had measurable disease. Seven different high-dose regimens were administered, even if 20 children received melphalan mostly associated with vincristine and 8 involved field radiotherapy. Three children died early of pneumonitis; 2 developed an acute transient renal failure, 1 a chronic renal failure. Out of the 8 children with target disease at graft, 2 died of toxicity, 5 achieved CR, 1 obtained PR, and only 1 is presently alive in CCR at 39 months after ABMT. Of the 17 children grafted in CR, 8 are alive event-free at 14-90 months (median 34) from ABMT; 7 relapsed at 3-23 months (median 7 months); 1 died of toxicity and 1 was lost to follow-up in CR at 12 months. A salvage attempt with high-dose chemotherapy in children with resistant or poor prognosis recurrent Wilms' tumor seems to be justified. An international cooperative protocol taking into account the increased risk of lung and renal toxicity is necessary.

Adolescent↗
PubMed1987

Bone marrow transplantation in multiple myeloma: report from the European Cooperative Group for Bone Marrow Transplantation.

Of 14 patients who received an allogeneic bone marrow graft from HLA-compatible sibling donors, 10 have survived for 6 to 34 months posttransplantation (median, 12 months). Four patients have died, two of relapse at extramedullary sites, one of severe acute GVHD, and one from GI bleeding and pericardial effusion. One patient is alive in relapse and four patients have signs of minimal persistent disease. Five patients are well without signs of active disease. Minor improvement in osteolytic lesions on X-ray were seen in three patients, but the X-ray bone structure was mainly unchanged in most patients. Bone marrow transplantation appears promising for treatment of certain patients with multiple myeloma.

Adult↗
PubMed2001

Impact of donor type on outcome of bone marrow transplantation for Wiskott-Aldrich syndrome: collaborative study of the International Bone Marrow Transplant Registry and the National Marrow Donor Program.

Human leukocyte antigen (HLA)-identical sibling bone marrow transplantation is an effective treatment for Wiskott-Aldrich syndrome. However, most children with this disease lack such donors and many patients receive transplants from alternative donors. This study compared outcomes of HLA-identical sibling, other related donor, and unrelated donor transplantation for Wiskott-Aldrich syndrome. The outcome of 170 transplantations for Wiskott-Aldrich syndrome, from 1968 to 1996, reported to the International Bone Marrow Transplant Registry and/or National Marrow Donor Program were assessed. Fifty-five were from HLA-identical sibling donors, 48 from other relatives, and 67 from unrelated donors. Multivariate proportional hazards regression was used to compare outcome by donor type and identify other prognostic factors. Most transplant recipients were younger than 5 years (79%), had a pretransplantation performance score greater than or equal to 90% (63%), received pretransplantation preparative regimens without radiation (82%), and had non-T-cell-depleted grafts (77%). Eighty percent received their transplant after 1986. The 5-year probability of survival (95% confidence interval) for all subjects was 70% (63%-77%). Probabilities differed by donor type: 87% (74%-93%) with HLA-identical sibling donors, 52% (37%-65%) with other related donors, and 71% (58%-80%) with unrelated donors (P =.0006). Multivariate analysis indicated significantly lower survival using related donors other than HLA-identical siblings (P =.0004) or unrelated donors in boys older than 5 years (P =.0001), compared to HLA-identical sibling transplants. Boys receiving an unrelated donor transplant before age 5 had survivals similar to those receiving HLA-identical sibling transplants. The best transplantation outcomes in Wiskott-Aldrich syndrome are achieved with HLA-identical sibling donors. Equivalent survivals are possible with unrelated donors in young children.

Actuarial Analysis↗
PubMed1982

Polyclonal antibody synthesis by bone marrow cells of New Zealand Black mice. II. Cellular basis of PAS activity of NZB bone marrow cells.

In the preceding report, enhanced polyclonal antibody synthesis (PAS) activity of bone marrow cells (BMC) of NZB mice was shown. Cells involved in its activity among BMC population were explored in this report. Antibody-forming cells (AFC) already existing in the bone marrow were not responsible for this activity since depletion of AFC by passage through a Sephadex G-10 column did not affect the numbers of anti-TNP AFC and immunoglobulin-secreting cells (IgSC) in the spleen of BMC-reconstituted mice when assayed 7 days after the transfer. Thy-1-positive cells among BMC population and host thymus were not relevant to PAS. Suppressor cells seemed to play little role as observed in transfer of mixed BMC population from NZB and BALB/c mice. PAS activity was prominently observed in surface immunoglobulin-positive cells. Significance of enhanced PAS activity was discussed with reference to autoantibody production.

Animals↗
PubMed1986

Acute folic acid deficiency after bone marrow transplantation.

After bone marrow transplantation (BMT), megaloblastic bone marrow changes are often observed that can only be partially explained by drug effects. Our goal was to find out whether folic acid deficiency represented an additional factor. The serum folic acid concentrations of 41 patients were determined regularly before and after BMT. A 2nd degree polynomial regression analysis revealed a clear and acute drop in folic acid concentrations within 7-9 days after BMT. In 19 patients the level fell below 3.0 ng/ml, the range of folic acid deficiency. The mean folic acid values without oral administration of folic acid after BMT lay significantly below the mean values with substitution (P less than 0.001). If a case of acute graft versus host disease (GvHD) was more severe than grade I, the mean folic acid levels were significantly lower (P less than 0.01). Patients with megaloblastic bone marrow changes after BMT had significantly lower folic acid values than those without such changes (P less than 0.01). The 18 patients with folic acid deficiency had a significantly higher rate of megaloblasts, binucleate erythropoietic precursors, Howell-Jolly bodies, giant myelocytes, and giant metamyelocytes in bone marrow smears than the remaining 23 patients (P less than 0.05). Folic acid deficiency did not slow down the increase in leukocytes, granulocytes, thrombocytes, or reticulocytes after BMT. There were 8.2%-9.7% hypersegmented neutrophils in the blood (normal 5%) after BMT both with and without folic acid deficiency. Folic acid deficiency after BMT was caused by insufficient intake combined with simultaneous decreased intestinal resorption and increased requirements for the regeneration of bone marrow and intestinal mucosa.

Adolescent↗
PubMed1992

Bone marrow plays a role in bone metabolism: histomorphometry of iliac bone in postmenopausal women.

We conducted a histomorphometrical study on the role of the bone marrow in cancellous bone metabolism using iliac bone specimens from 79 postmenopausal women. A gradual decrease in hematopoietic tissue of the bone marrow was proportionate to the decrease in cancellous bone and the ratio of osteoid perimeter/bone perimeter regardless of age. On the other hand, the ratio of eroded perimeter/bone perimeter remained almost steady until hematopoietic tissue decreased significantly. These findings suggest that a change in the bone marrow, that is, a decrease in hematopoietic tissue, causes an imbalance in bone formation and resorption and leads to bone loss.

Aged↗
PubMed1991

Autologous bone marrow transplantation for acute myeloblastic leukemia in Europe: further evidence of the role of marrow purging by mafosfamide. European Co-operative Group for Bone Marrow Transplantation (EBMT).

Fifty-nine European teams have reported 919 autografts for the consolidation of acute myelocytic leukemia (AML) up to December 31, 1989. The distribution for autologous bone marrow transplantation (ABMT) was 671 in first complete remission (CR1) and 196 in CR2. Pretransplantation regimes were: total-body irradiation (TBI), 456; busulfan plus cyclophosphamide (BU-CY) 174; marrow purging with mafosfamide, 269 (corresponding to 26% of all patients in CR1 and 41% in CR2). Patients autografted in CR1 with no high risk factor (standard risk) had a leukemia-free survival (LFS) and relapse rate at 7 years of 48 +/- 2 and 41 +/- 3%, respectively. Of all the prognostic factors studied, only secondary leukemia was correlated with a poorer LFS (19 +/- 9% at 1 year) and a higher relapse rate (76 +/- 11%) (p less than 0.0001). For patients autografted in CR2, the LFS and relapse rate were 34 +/- 4 and 54 +/- 5%. With the restriction of a shorter follow-up, the results achieved with the BU-CY combinations (LFS and relapse rate at 3 years, CR1 47 +/- 6 and 45 +/- 7%; CR2, 37 +/- 9 and 50 +/- 10%) did not differ from those with TBI or other chemotherapy combinations. LFS and relapse rates were correlated with several pretransplant intervals: in CR1, patients reaching CR more rapidly (less than or equal to 40 days) had a better LFS (53 +/- 3 versus 42 +/- 3%; p = 0.03) and a lower relapse rate (46 +/- 3 versus 57 +/- 3%; p = 0.03). In patients autografted less than 3 months, 3-6 months and more than 6 months after CR, the LFS was 26 +/- 5, 49 +/- 3, and 55 +/- 4%, respectively, and the relapse rates 63 +/- 5, 38 +/- 3, and 36 +/- 4% (p less than 0.0001 for both). In CR2, patients autografted more than 18 months after the initial diagnosis had a better LFS (42 +/- 5 versus 24 +/- 5%; p less than 0.001) and a lower relapse rate (45 +/- 6 versus 65 +/- 6%; p less than 0.001). For those autografted less than 3 months, 3-6 months and more than 6 months after CR, the probability of LFS was 30 +/- 5, 30 +/- 7, and 50 +/- 9% (p = 0.06), respectively and the relapse rates 63 +/- 6, 50 +/- 8, and 36 +/- 8% (p = 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗