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.     

Asthma vs. non-specific reversible airflow obstruction: clinical features and responsiveness to anticholinergic drugs

85 subjects with 20% reversibility in FEV1 were classified into the categories of asthma (55 patients) and non-specific airflow obstruction (30 patients), respectively, on the basis of the presence or absence of eosinophilia (in the blood or sputum). Asthmatics were further subdivided into the atopic and non-atopic subgroups, respectively, on the basis of skin prick tests. Clinically, paroxysmal nocturnal wheezing was more significantly associated with asthma than with non-specific airflow obstruction. Atopic asthmatics were distinguished from patients with non-specific airflow obstruction by their younger age at presentation and at onset of obstructive symptoms, by a history of allergic provocation of wheezing, a family history of asthma and other atopic diseases, and by a lower incidence of mucus hypersecretion. The last 3 symptoms also distinguished atopic from non-atopic asthma. Furthermore, unlike patients with non-atopic asthma or patients with non-specific airflow obstruction, atopic asthmatics had a significant impairment of bronchodilator responsiveness to inhaled anticholinergic drugs.     

Variability in 4-hydroperoxycyclophosphamide activity during clinical purging for autologous bone marrow transplantation

We examined the effects of varying incubation conditions on the in vitro activity of 4-hydroperoxycyclophosphamide (4HC). 4HC activity against CFU-GM and against the K562 tumor cell line decreased with increasing the RBC concentration of the incubation mixture. Increasing the concentration of nucleated bone marrow cells in the incubation mixture also decreased the 4HC activity. Evaluation of 53 consecutive patients undergoing autologous bone marrow transplantation (BMT) revealed that the incubation RBC concentration during clinical purging showed a similar effect on CFU-GM recovery. Aldehyde dehydrogenase content of RBCs and nucleated marrow cells appears to be the cause of the inhibition of 4HC activity. Although there was no difference in individual CFU-GM sensitivity to 4HC among normals, previously treated patients undergoing autologous BMT showed significant variability in CFU-GM sensitivity to 4HC. The combined effects of incubation RBC concentration and individual patient 4HC sensitivity appear to account for most of the variability in CFU-GM recovery and speed of hematologic recovery after clinical purging with 4HC.     

Efficacy of ex vivo purging for autologous bone marrow transplantation in the treatment of acute nonlymphoblastic leukemia

We used an in vitro measure of drug activity to predict the efficacy of ex vivo purging of leukemic cells from autologous bone marrow grafts. We previously found that the myeloid progenitor cell (CFU-GM) content of the marrow grafts after ex vivo purging with 4- hydroperoxycyclophosphamide (4-HC) correlates with time to hematologic recovery after autologous bone marrow transplantation in patients with acute nonlymphoblastic leukemia. We observed that variable red blood cell concentration of the bone marrow incubation mixture results in differential cytotoxic activity of 4-HC. The CFU-GM content of the graft after the ex vivo treatment is a measure of this 4-HC activity. We analyzed the disease-free survival of 45 patients with acute nonlymphoblastic leukemia undergoing autologous bone marrow transplantation with 4-HC purged grafts. Patients who relapsed after transplantation had 4.2 +/- 1.1% of graft CFU-GM surviving the ex vivo purge, compared with 1.1 +/- 0.4% for patients who achieved a sustained remission (P = .06). Twenty-three patients with a CFU-GM content after 4-HC purging of greater than 1% of the pretreatment value had an actuarial disease-free survival of 12%, compared to 36% for 22 patients with a less than or equal to 1% CFU-GM content after purging (P = .006). Therefore, percent CFU-GM survival as a measure of 4-HC cytotoxicity identified a group of patients with insufficient purging. Although no randomized clinical trials have documented the need for ex vivo purging, our results suggest that effective bone marrow purging is important for the optimal application of autologous transplantation in the treatment of acute nonlymphoblastic leukemia.     

Role of malaria induced oxidative stress on anaemia in pregnancy

ObjectiveTo assess the role of oxidative stress on anaemia in pregnancy.MethodsBlood samples were collected from pregnant and non-pregnant women who came for antenatal clinic and medical check at Comprehensive Health Center, Akungba-Akoko and Iwaro General Hospital in Akoko Area of Ondo State, Nigeria. Thick and thin blood films were prepared and used for malaria parasite counts. Haemoglobin level was determined by colorimetric method using Drabkin's solution. Oxidative status was determined using malondiadelhyde level as an indicator of lipid peroxidation, while ascorbic acid and reduced glutathione levels were measured by standard spectrophotometric methods.ResultsMean parasite density was significantly higher in pregnant women than non-pregnant women (P<0.05). Haemoglobin level was significantly reduced in malaria positive pregnant and non-pregnant women than malaria negative (8.3-10.0 g/dL) (P<0.05). The oxidative status indicated that malondialdehyde (MDA) was significantly increased in pregnant [(2.5±0.7) nmol/mL] than non-pregnant women [(1.8±0.1) nmol/mL] (P<0.05), while Vit C and superoxide dismutase (SOD) levels were significantly reduced in pregnant than non-pregnant women(P<0.05). There was an inverse correlation between Hb and MDA levels in pregnant women studied. Positive correlation was observed between the mean MDA level and parasite density (r = 0.53). The Hb level decreased as the parasite density and MDA level increased in pregnant women.ConclusionsThis study shows that oxidative stress, caused by malaria infection could be part of the contributing factors responsible for anaemia in pregnancy.