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[Evolutionary and bone marrow recovery indicators in bone marrow transplantation after total body irradiation].

Oxidative stress and reticulocyte maturity index (RMI) were studied in 27 patients who underwent bone marrow transplantation (BMT). Plasmatic lipoperoxide levels of those patients with unfavorable evolution were significantly increased on days 12-14 post-transplant (median 1.83 microM, range 0.78-5.82) compared with preconditioning levels (median 1.05 microM, range 0.36-1.84) (p < 0.05). Patients with favorable evolution revealed significantly higher lipoperoxide levels during conditioning regime (median 1.42 microM, range 0.31-4.50) (p < 0.05). Starting from the 3rd post-transplant week a significant and continuous decrease was observed, with a median of 0.77 microM (range 0.21-1.48 p < 0.05) for the 3rd, and a median of 0.60 microM (range 0.11-1.48 for the 4th week (p < 0.01). A significant increase in total antioxidant activity was observed in the three patients who died up to the 35 days post-transplant. Recovery of bone marrow function was detected by RMI after a median time of 17 days (range 11-24) post-allogeneic transplantation. The threshold established for absolute neutrophil count was achieved after a median of 21 days (range 14-28) (p < 0.001). An increase of plasma lipoperoxides on days 12-14 post-transplant may be a predictive value of unfavourable evolution. RMI was the earlier indicator of engraftment in allogeneic BMT.

Adolescent↗

Peroxidase activation of hydroquinone results in the formation of DNA adducts in HL-60 cells, mouse bone marrow macrophages and human bone marrow.

Metabolism of benzene results in the formation of multiple metabolites, including hydroquinone (HQ). HQ is a reducing co-substrate for peroxidase enzymes, and the resultant semiquinone and para-benzoquinone (p-BQ) may bind to DNA. The role of peroxidase activation in the formation of DNA adducts by benzene metabolites has not been established. In this study we investigated the role of peroxidase activation in the formation of DNA adducts by HQ and p-BQ in HL-60 cells, human bone marrow (HBM) cells, mouse bone marrow macrophages (MBMM) and the U-937 and Raji leukemia cell lines. Adduct formation was measured by P1-enhanced 32P-postlabeling; peroxidase activity was measured with a spectrophotometric assay. Treatment with p-BQ resulted in the formation of two DNA adducts in all of the cell lines. The DNA adducts were identical in all of the cells, however, the adduct level varied by 80-fold. Treatment with HQ produced one DNA adduct in HL-60 cells, HBM and MBMM; no adducts were detected in U-937 or Raji cells. The HQ-DNA adducts in the three cell lines were identical. The adduct level was highest in the HL-60 cells, followed by HBM and MBMM. There was a statistically significant correlation between peroxidase activity and the formation of HQ-DNA adducts. These results suggest that peroxidase-mediated metabolism is involved in the activation of HQ to form DNA adducts in mouse bone marrow and HBM.

Animals↗

Regulation of constitutive bone marrow cell proliferation by bone marrow suppressor cells.

Bone marrow (BM) cells have previously been shown to suppress specific immune responses of cells from peripheral lymphoid organs. The present report describes a suppressor cell present in normal rabbit BM, which regulated the constitutive proliferation of other BM cells. The suppressor cells were Fc gamma-receptor-positive (Fc gamma R+) complement-receptor-negative, and nonadherent or weakly adherent. Similar suppressive activity was not detected among rabbit spleen cells. Removal of Fc gamma R+ suppressor cells allowed greater than 10-fold increases in the proliferation of Fc gamma R- BM cells. Addition of Fc gamma R+ BM cells to Fc gamma R- cells efficiently blocked proliferation. The suppressor cells acted by inhibiting the elaboration of a soluble growth-promoting factor by cells in the Fc gamma R- population. The growth-promoting factor enhanced proliferation of unseparated rabbit BM cells and peripheral blood mononuclear cells.

Animals↗

CFU-GM content of bone marrow graft correlates with time to hematologic reconstitution following autologous bone marrow transplantation with 4-hydroperoxycyclophosphamide-purged bone marrow.

Autologous bone marrow transplants (BMTs) can repopulate the hematologic system of patients treated with marrow-ablative chemotherapy and/or radiotherapy. However, treatment of the bone marrow graft to eliminate residual tumor cells prior to reinfusion can delay the return of peripheral blood elements, presumably from damage to or loss of hematopoietic stem cells responsible for hematologic recovery. To develop a model predictive of hematologic recovery, we studied the progenitor cell contents of 4-hydroperoxycyclophosphamide (100 micrograms/mL)-purged bone marrow grafts of 40 consecutive patients undergoing autologous BMT at this center. Granulocyte-macrophage colonies (CFU-GM) were grown from all grafts after treatment with this chemotherapeutic agent, but erythroid (BFU-E) and mixed (CFU-GEMM) colonies were grown from only 44% and 33% of the grafts respectively. The recovery of CFU-GM after purging ranged from 0.07% to 23%. The logarithm of CFU-GM content of the treated grafts was linearly correlated with the time to recovery of peripheral blood leukocytes (r = -0.80), neutrophils (r = -0.79), reticulocytes (r = -0.60), and platelets (r = -0.66). The CFU-GM content of purged autologous bone marrow grafts may reflect the hematopoietic stem cell content of the grafts and thus predict the rate of hematologic recovery in patients undergoing autologous BMT.

Adolescent↗

Treatment of bone marrow aplasia by mismatched bone marrow transplantation after conditioning with antilymphocyte globulin--long-term results.

Twenty patients with very severe bone marrow aplasia were treated with mismatched bone marrow transplants. Engraftment and transitory chimerism (from 2-10 months) not complicated by secondary disease occurred in 4 patients. Of these, 3 are still alive after 5 years, with a compensated hematologic status. Engraftment failed in 16 patients; only 1 of these is still alive after 5 years.

Anemia, Aplastic↗

A modified method for human bone marrow filtration prior to bone marrow transplantation.

A technique is described for filtering harvested bone marrow using disposable materials, namely a 4 x 4 inch piece of sterile gauze that is gently packed into the barrel of a 60-ml plastic disposable syringe, which is connected directly to a blood collection bag. The filtration of marrow directly into the collection bag eliminates additional filtration steps and therefore may potentially reduce the incidence of inadvertent microbial contamination. In this study we describe this filtering technique and compare it to the method described by Thomas and Storb. Numbers of granulopoietic progenitors (CFU-GM) and erythropoietic progenitors (BFU-E), total white cell counts, percentage of cells positive for the CD3 (OKT3) lymphocyte surface membrane marker, and volume changes were studied following filtration by each method. The two techniques were shown to be comparable in terms of these parameters. Furthermore, when compared with historical controls, this method resulted in a reduced incidence of microbial contamination compared to filtration using successive stainless steel screens.

Adolescent↗

A randomized trial of oral versus intravenous acyclovir for treatment of herpes zoster in bone marrow transplant recipients. Nordic Bone Marrow Transplant Group.

Twenty-seven bone marrow transplant patients who developed localized herpes zoster were treated with acyclovir in a randomized study comparing oral and intravenous drug administration. Fourteen patients received oral and 13 patients received intravenous treatment. None of the patients developed disseminated disease. No differences were found between the treatment groups in the number of days that new lesions continued to develop, in number of days with pain, or in the number of days from start of treatment until all lesions were crusted over. We suggest that oral acyclovir may be as effective as intravenous acyclovir in the treatment of localized herpes zoster after bone marrow transplantation.

Acyclovir↗

[Treatment of bone marrow aplasia by allogenic bone marrow grafts].

Three patients with severe aplastic anemia were treated by bone marrow transplantation using the method described by Santos and Thomas. Two of the patients, both successfully grafted have survived for more than 5 and 6 months respectively. Chimerism was proved by cytogenetic analysis and erythrocytic phenotypes. In one case, a severe graft versus host reaction was cured with ATG and prednisone. Graft rejection in the third case was related to the immunisation caused by many previous transfusions. Although bone marrow grafting is limited by the necessity of using a matched sibling as donor, its success this far is very encouraging and represents a new hope for the treatment of aplastic anemia.

Adolescent↗

Bone marrow biopsy (BMB). III. Bone marrow biopsy in Hodgkin's disease (HD).

Bone marrow biopsies have been investigated in 330 cases of Hodgkin's disease totalising 298 patients, out of which 32 with repeated biopsies. Positive biopsies with typical lesions were found in 32% of patients, the majority in stages III and IV (88.6%), rarely in stage I or II (11.4%). Nonspecific lesions were very frequent (75%), either isolated or accompanied by typical lesions. The majority of the positive biopsies were found in patients with lymphocytic predominance and lymphocytic depletion, or in polytreated patients in an advanced stage of the disease. The specific marrow involvement consisted in lymphocytic infiltrations either nodular or diffuse, Reed-Sternberg (R-St) or Hodgkin cells. The lymphocytic depletion is often accompanied by diffuse fibrosis, atypical histiocytes, fibroblasts and R-St cells. Hodgkin typical granulomas are rare. The positive biopsies were associated with nonspecific reactions including hyperplasia of granulopoiesis, megakaryocytes, territories with hyperplasia or aplasia, fibrosis, disruption of sinus walls, oedema, plasmocytosis, necrosis, myelomonoblastic cells, lymphocyte nodes, etc. The bone marrow histology has a prognostic significance.

Biopsy↗

The use of bone-marrow-derived fibroblastoid cells and fresh bone marrow in the treatment of bone defects: an experimental study.

Bone-marrow aspirate (containing bone progenitor cells), in vitro expanded autologous bone-marrow-derived stromal fibroblastoid cells, and a combination thereof were tested for the potential to fill bone defects. They were compared to grafts of fresh autologous bone or allogeneic devitalized bone. Mandibular defects in rabbits were chosen for this study. The best results were obtained with a combination of in vitro expanded bone-marrow-derived stromal fibroblastoid cells and fresh autologous bone marrow or fresh autologous marrow alone. The effects of these two grafts were similar to grafts of fresh autologous bone and significantly superior to grafts of devitalized allogeneic bone providing only a bone matrix. The in vitro expanded marrow stromal cells induced very significant bone ingrowth, and their effects were only slightly inferior to fresh autologous bone but were superior to devitalized allogeneic bone. These studies suggest that bone marrow is a good source of osteogenic cells both for immediate transplantation and for in vitro expansion and subsequent transplantation.

Animals↗

Analyzing the cellular contribution of bone marrow to fracture healing using bone marrow transplantation in mice.

The bone marrow is believed to play important roles during fracture healing such as providing progenitor cells for inflammation, matrix remodeling, and cartilage and bone formation. Given the complex nature of bone repair, it remains difficult to distinguish the contributions of various cell types. Here we describe a mouse model based on bone marrow transplantation and genetic labeling to track cells originating from bone marrow during fracture healing. Following lethal irradiation and engraftment of bone marrow expressing the LacZ transgene constitutively, wild type mice underwent tibial fracture. Donor bone marrow-derived cells, which originated from the hematopoietic compartment, did not participate in the chondrogenic and osteogenic lineages during fracture healing. Instead, the donor bone marrow contributed to inflammatory and bone resorbing cells. This model can be exploited in the future to investigate the role of inflammation and matrix remodeling during bone repair, independent from osteogenesis and chondrogenesis.

Animals↗