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Safety and efficacy of spinal vs general anaesthesia in bone marrow harvesting.

Bone marrow harvesting (BMH) can be performed with either general (GA) or spinal anaesthesia (SPA). Whether SPA is advantageous in BMH and if this technique is safe for procedures performed in the prone position is still controversial. To evaluate the safety and efficacy of both anaesthetic techniques in BMH, 37 allogeneic donors (nine female, 28 male; 34.3 +/- 9 years; ASA class 1-2) received either spinal (group 1, n =20) or general anaesthesia (group 2, n = 17) according to their personal wishes. Under standardised harvesting conditions, haematology parameters, cell counts (MNC, CD34+), haemodynamic parameters, adverse reactions and patient satisfaction were registered. No differences were seen between groups with respect to demographic data, harvesting time (55 +/- 17 vs 60 +/- 16 min) and bone marrow cell counts (MNC: 6.68 +/- 2.1 vs 5.7 +/- 1.7 ml/10(6)). The incidence of hypotension was higher in group 1 (45 vs 10.8%; P =0.042). Postoperative analgesic requirement and emesis were increased in group 2 (P < 0.04) in comparison to group 1. In conclusion, the present study failed to show superiority of spinal over general anaesthesia with regard to the quality of the harvested bone marrow. However, the lower incidence of complaints after spinal anaesthesia appears to offer an advantage over GA in healthy allogeneic bone marrow donors.

Adult↗

Induction of erythropoietin responsiveness in vitro by a distinct population of bone marrow cells.

Bone marrow contains a small population of primitive erythroid progenitor cells which can be detected by their capacity to form large numbers of erythroid progeny in viscous cultures containing erythropoietin (EP). These cells have been termed erythroid 'burst-forming units' (BFUe). The present study demonstrates that expression of the erythroid differentiation potential of BFUe requires the presence of an activity additional to EP. This activity has been designated as BFA (burst feeder activity). It is shown that the number of BFUe detected and their apparent sensitivity to EP are directly related to the BFA concentration of the cultures. BFA was found to be associated with a population of bone marrow cells of high buoyant density and small volume, which are sensitive to irradiation. The radiation dose-effect curve provided strong evidence that bone marrow BFA is independent of cell proliferation; this was supported by showing that BFA is unaffected by in vivo treatment with hydroxyurea. The findings are compatible with a two-step regulation model for erythroid differentiation in which BFA-induced progeny of BFUe acquire sensitivity to EP.

Animals↗

Bone marrow transplantation in New Zealand. New Zealand Bone Marrow Transplant Study Group.

From their initiation in 1979 until the end of 1992, five New Zealand transplant centres have carried out a total of 233 bone marrow transplants, of which 149 were allografts and 84 autografts. The New Zealand Bone Marrow Transplant Study Group aims to coordinate the transplant programmes and maintains a collaborative register of transplants. This report provides a brief overview of transplantation activity within New Zealand and summarises the results.

Anemia, Aplastic↗

Graft-versus-leukemia in bone marrow transplantation. The Advisory Committee of the International Bone Marrow Transplant Registry.

We studied 2254 persons receiving HLA-identical sibling bone marrow transplants for acute myelogenous leukemia (AML) or acute lymphoblastic leukemia (ALL) in first remission, or chronic myelogenous leukemia (CML) in first chronic phase to determine whether graft-versus-leukemia (GvL) reactions are important in preventing leukemia recurrence after bone marrow transplantation. Four groups were investigated; recipients of non-T-cell depleted allografts without graft-versus-host disease (GvHD), recipients of non-T-cell depleted allografts with GvHD, recipients of T-cell depleted allografts, and recipients of genetically identical twin transplants compared with recipients of non-T-cell depleted allografts without GvHD, Decreased relapse was observed in recipients of non-T-cell depleted allografts with acute (relative risk 0.68, P = 0.03), chronic (relative risk, 0.43, P = 0.01), and both acute and chronic GvHD (relative risk 0.33, P = 0.0001). These data support an anti-leukemia effect of GvHD. AML patients receiving identical twin transplants had an increased probability of relapse (relative risk 2.58, P = 0.008) compared to allograft recipients without GvHD supporting an anti-leukemia effect of allografts independent of GvHD. CML patients receiving T-cell depleted transplants without GvHD had a higher probability of relapse (relative risk 6.91, P = 0.0001) than recipients of non-T-cell depleted allografts without GvHD. These data support an antileukemia effect independent of GvHD altered by T-cell depletion. These results indicate that much of the anti-leukemia effect of bone marrow transplants is related to immune factors rather than high-dose chemotherapy and/or radiation.

Bone Marrow Transplantation↗

An appraisal of the value of the bone marrow biopsy in the assessment of proliferative lesions of the bone marrow.

The diagnostic value of the bone marrow needle biopsy has proved impressive in a variety of disorders. As a complementary procedure to the aspiration smear it adds an invaluable dimension to the examination of haematopoietic tissue. The procedure is easily learned and safe and should be utilized routinely in haematological practice. The usefulness of the bone marrow biopsy is examined in assessing proliferative lesions of the bone marrow.

Biopsy, Needle↗

Bone marrow involvement by non-Hodgkin's lymphoma: the clinical significance of morphologic discordance between the lymph node and bone marrow. Nebraska Lymphoma Study Group.

Bone marrow specimens from 317 patients with non-Hodgkin's lymphoma (NHL) obtained at initial staging were evaluated for the presence of lymphoma or benign lymphoid aggregates. Thirty-two percent (102 patients) had lymphoma in their bone marrow, and 9% had benign lymphoid aggregates. Bone marrow lymphoma was present in 39% of low-grade, 36% of intermediate-grade, and 18% of high-grade lymphomas. The bone marrow was involved in 25% of patients with diffuse large-cell or immunoblastic NHL (ie, diffuse histiocytic lymphoma of Rappaport). Bone marrow involvement did not affect survival of patients with low-grade NHL, but survival was significantly shorter (P = .03) for patients with intermediate- and high-grade NHL with bone marrow involvement. Bone marrow involvement was equally common in B-cell and T-cell NHL (31% v 32%). However, patients with T-cell NHL and bone marrow involvement had shorter survival than B-cell NHL with marrow involvement (P = .02) or T-cell NHL without marrow involvement (P = .05). A high incidence of morphologic discordance between lymph node and bone marrow was observed (ie, 40%), always with a more aggressive subtype in the lymph node than in the bone marrow. Presence of large-cell lymphoma in the bone marrow predicted for short survival. Survival for patients with small-cell lymphoma in their bone marrow did not differ significantly from patients with negative bone marrows. We conclude that bone marrow involvement in large-cell NHL, especially in those of T-cell origin, portends a poor prognosis. However, the subgroup of patients with an aggressive histologic subtype of NHL in a lymph node biopsy and small-cell NHL in the bone marrow do not have a poorer outlook than those without bone marrow involvement.

Actuarial Analysis↗

Development of monoclonal antibodies to erythroid progenitors in feline bone marrow.

Feline bone marrow cells can be enriched for erythroid and myeloid progenitors by counterflow centrifugal elutriation (CCE) and subsequent treatment of the CCE fractions with the soybean agglutinin (SBA) lectin. Separation of CCE fractions into SBA(-) and SBA(+) populations yielded cells enriched for BFU-E and CFU-GM progenitors, respectively. Differential analyses revealed a high percentage of erythroid lineage cells in the SBA(-) fractions and in the SBA(+) fractions a high concentration of myeloid cells of varying maturation stages. The latter cells, but not the CFU-GM progenitors, could be removed by immunomagnetic depletion from CCE fractions using a monoclonal antibody (MAb) specific for CD13 cells in feline bone marrow, resulting also in a population containing predominantly erythroid differentiating cells. Mice were immunized with CCE fractions enriched for erythroid lineage cells and the splenocytes fused with SP2/O cells for hybridoma development. Supernatant culture fluids from 400 hybridomas were analyzed by flow cytometry with whole bone marrow and select CCE/SBA fractions as the target cells. Those hybridomas suggestive of containing the desired antibodies as indicated by the percentage staining were subcloned and the MAbs utilized in clonogenic assays. Treatment of bone marrow cells or CCE fractions with the MAbs followed by immunomagnetic depletions led to identification of two, K-1 and Q-3, reactive with the BFU-E progenitor and one, K-7, reactive only with late-differentiating erythroid lineage cells. Thus, removal of cells from a CCE/SBA suspension reactive with K-1 or Q-3 led to greater than 80% reductions of the BFU-E progenitors and a population enriched for CFU-GM. Removal of cells reactive with MAb K-7, however, led to a marked enrichment, 5-8-fold, of both BFU-E and CFU-GM progenitors.

Animals↗

Analysis of the origin of marrow cells in bone marrow transplant recipients using a Y-chromosome-specific in situ hybridization assay.

A Y-chromosome-specific in situ hybridization assay was used to assess the frequency with which host bone marrow cells are retained after marrow grafting. The majority of patients (74%) showed the presence of both host and donor marrow cells when assayed 14 days after transplant. By 84 days posttransplant only 4% of the patients retained host marrow cells. Only 1 of 19 evaluable patients analyzed over 1 year posttransplant showed minimal retention of host cells. No statistical correlation was found between retention of host cells posttransplant and the development of relapse or acute or chronic graft-versus-host disease. Pretransplant conditioning regimen, HLA-matching, diagnosis, disease status at transplant, ABO-matching, and patient age also showed no correlation with the retention of host cells posttransplant.

Bone Marrow Cells↗

Complete remission of tumour with interleukin 2 therapy in a patient with non-Hodgkin's lymphoma post allogeneic bone marrow transplant associated with polyclonal T-cell bone marrow lymphocytosis.

A patient with low-grade non-Hodgkin's lymphoma (NHL) who relapsed shortly after an allogeneic bone marrow transplant (BMT) is reported. The patient was treated with interleukin 2 (IL-2), which resulted in a flare-up of graft-versus-host disease followed by disease control, with disappearance of peripheral lymphadenopathy. Sequential bone marrow testing showed the disappearance of bone marrow involvement with disease but occurrence of T-cell aggregates post IL-2 that were identified as polyclonal by molecular methods. The patient remains in complete remission 37 months following allogeneic BMT.

Antineoplastic Agents↗

[Treatment of stage IV neuroblastoma with high-dose melphalan and autologous bone marrow transplantation following in vitro preliminary treatment of the bone marrow with the active cyclophosphamide derivative Asta Z-7654].

The case of a 4 year 8 months old boy with neuroblastoma of unknown primary, metastatic to the bone and to the bone marrow is presented. After achieving a partial remission with six cycles of conventional chemotherapy, the patient was given supraconventional chemotherapy (melphalan 220 mg/m2 bolus i.v.) in an effort to eliminate residual disease. Prior to the administration of the drug, 560 cc of autologous bone marrow, morphologically free of tumor was harvested (total 110 X 10(8) nucleated cells) and concentrated to a mononuclear cell fraction with a total of 10 X 10(8) cells. After in vitro purging with the stable metabolite of 4-hydroperoxycyclophosphamide ASTA Z 7654 (40 micrograms/2 X 10(7) mononuclear cells/ml), the mononuclear cell suspension was retransfused 10 hours following the application of high dose melphalan. Hemopoietic reconstitution was delayed with a platelet count reaching 70,000/microliter only after seven months. At the time of this writing (20 months after diagnosis and 16 months after autologous bone marrow transplantation) there is no evidence for active disease according to the bone scan and multiple bone marrow biopsies. In view of the dismal prognosis of patients with neuroblastoma, stage IV it is recommended that further patients should be treated with a slightly modified protocol of the cooperative austrian neuroblastoma study.

Antineoplastic Combined Chemotherapy Protocols↗

Bone marrow scintigraphy as a useful method for estimating the physiological status of bone marrow and spleen in polycythaemia vera.

Bone marrow scintigraphy is a simple and noninvasive examination useful to define the status of the bone marrow and spleen in polycythaemia vera (P.V.). Despite the absence of specificity of Indium 111 labelled transferrin (In-Tf) for myelopoietic tissue, there is a close correlation between bone marrow In-Tf uptake and bone marrow cellularity and between splenic In-Tf uptake and splenic metaplasia. The results of scintigraphy are compared to clinical data, radioactive iron kinetics, bone marrow and spleen histology and the course of the disease. The diagnostic and prognostic value of bone marrow scintigraphy is discussed, particularly at the stage of transformation of P.V. into postpolycythaemia myeloid metaplasia (Post-P.V.M.M.).

Bone Marrow↗

[The improving effect of bone marrow stromal cell transfected with IL-3 gene on hematopoietic reconstitution in bone marrow transplantation of mice].

To study the improving effect of regulatable gene of IL-3 engineered bone marrow stromal cell on the hematopoietic reconstitution in allogeneic bone marrow transplantation, an inducible gene expression system was established in a bone marrow stromal cell line which expressed IL-3 gene induced by doxycycline (Dox). The lethally irradiated mice C57BL/6 (H-2(d)) were co-transplanted with allogeneic bone marrow (BALB/c, H-2(d), 1 x 10(7)/mice) in which T cell were depleted by monoclonal antibody anti-Thy1.2 added with complement and the gene engineered stromal cell QXMSC1tet-on + IL-3 (5 x 10(5)/mice) at the same time. Dox was administrated continuously for 15 days to induce the expression of IL-3. The hematopoiesis in the bone marrow transplanted mice were observed at 30, 60 days post-transplantation, respectively. The numbers of RBC and WBC in peripheral blood were counted, and nucleated cells, CFU-S, CFU-GM, CFU-E and CFU-GEMM were measured in recipient bone marrow. The results showed that the engineered stromal cell line achieved high-level and controllable IL-3 expression. Co-graft with QXMSC1tet-on + IL-3 significantly increased the number of RBC, WBC in recipient peripheral blood, and the nucleated cells, CFU-S, CFU-GM, CFU-E, CFU-GEMM in bone marrow, compared with those coinfused with QXMSC1 or QXMSC1tet-on-TRE as control. In conclusion, regulatable gene IL-3 engineered bone marrow stromal cells accelerates hematopoietic reconstitution after allogeneic bone marrow transplantation.

Animals↗

Human bone marrow lymphocytes. III. Polyclonal activation of B lymphocytes in human bone marrow measured by a direct plaque-forming cell assay.

Lymphocytes from the bone marrow and peripheral blood of the same normal individuals were assayed simultaneously for blast transformation as well as polyclonal activation with differentiation to antibody-forming cells after stimulation with pokeweed mitogen. Blastogenic responses were measured by tritiated thymidine incorporation and antibody-forming cell assay. There was no significant difference between the blastogenic responses of lymphocytes in the peripheral blood compared to the bone marrow of the same individuals. However, differentiation to antibody-forming cells measured by the plaque-forming cell response was significantly greater in lymphocytes in the bone marrow as compared to peripheral blood of the same individuals. These studies demonstrate that the lymphocytes in human bone marrow are at a stage of differentiation whereby they can be readily induced to differentiation toward antibody production by polyclonal activation, even more so than peripheral blood lymphocytes. This supports the concept that the bone marrow is a major source of immunoglobulin production in man.

Adult↗