Sujata Mohanty

The ABCD (Autologous Bone Marrow Cells in Dilated Cardiomyopathy) trial a long-term follow-up study.

To the Editor:nnWe reported the short-term results (6-month follow-up) of a pilot study of the role of stem cell therapy in ischemic cardiomyopathy ([1][1]). We now present the final long-term (3-year follow-up) results of the trial. The study included patients between 15 and 70 years of age with

Response to Imatinib mesylate in chronic myeloid leukemia patients with variant BCR-ABL fusion transcripts

Chronic myeloid leukemia patients with different BCR-ABL transcripts might respond differently to Imatinib mesylate. This prompted us to study BCR-ABL transcripts in chronic myeloid leukemia (CML) patients and their correlation with response to Imatinib. Eighty-seven chronic phase CML patients (median age, 35xa0years; range, 13–62xa0years; M/F, 59:28) were included in this study; 57 patients had received interferon-α and/or hydroxyurea, and 30 were previously untreated. All patients received Imatinib mesylate (Gleevec) 400xa0mg daily. Complete hematological remission rate and major cytogenetic response (CGR) rates were 99% and 72%, respectively. B3a2 transcript was present in 53% of patients, b2a2 in 39%, and both transcripts in 8% of patients. Twenty of 34(59%) patients with b2a2 type achieved complete CGR compared to 15 of 53 (28%) patients with b3a2, pu2009=u20090.04. Among 24 patients with minor or no CGR, six (25%) had b2a2 compared to 18 (75%) b3a2 type, pu2009=u20090.04. Expression of BCR-ABL/ABL% was higher in b3a2 patients compared to b2a2, pu2009=u20090.120. Pre-treatment characteristics—mean spleen size (6.6 vs. 6.4xa0cm, pu2009=u20090.868), mean hemoglobin (G/dl; 12.0 vs. 11.8, pu2009=u20090.690), mean WBC count (83u2009×u2009109 vs. 77u2009×u2009109/L, pu2009=u20090.923), and mean platelets counts (360x109 vs. 340u2009×u2009109/L, pu2009=u20090.712)—were not significantly different in the b3a2 vs. b2a2 transcripts groups. Our preliminary findings suggest that CML patients with b2a2 BCR-ABL transcript might have higher CGRs to Imatinib mesylate (Gleevec).

Pathogenetic factors underlying juvenile deep vein thrombosis (DVT) in Indians

Abstract: The role of hereditary antithrombotic protein defects in juvenile deep vein thrombosis (DVT) was evaluated. Fifty six young patients (age <45 yr) with doppler‐proven DVT were investigated for the presence of resistance to activated protein C (APC‐R), lupus anticoagulant (LA), anticardiolipin antibodies and deficiencies of protein C, protein S, ATIII activities. Fifty nine normal healthy individuals served as controls. APC‐R was observed to be the commonest defect underlying the Indian DVT as seen in 39.2% of patients followed by elevated ACA (5.3%), PAI (2.8%), presence of LA (2.8%) and reduced ATIII levels (2.8%). None of the subjects had protein C or S deficiency. APC‐R was associated with ATIII deficiency in one case, and elevated ACA in two cases. In two subjects, APC‐R was associated with elevated PAI levels. Patients with more than one prothrombotic factor had a higher prevalence of pulmonary thromboembolism, suggesting that the thrombogenic potential of APC‐R is enhanced by the presence of coexisting hereditary or acquired prothrombotic defect.

Mobilization of Stem Cells Using G-CSF for Acute Ischemic Stroke: A Randomized Controlled, Pilot Study

Background. There is emerging evidence to support the use of granulocyte colony-stimulating factor (G-CSF) therapy in patients with acute ischemic stroke. Aims. To explore feasibility, safety, and preliminary efficacy of G-CSF therapy in patients with acute ischemic stroke. Patients and Method. In randomized study, 10 patients with acute ischemic stroke were recruited in 1u2009:u20091 ratio to receive 10u2009μg/kg G-CSF treatment subcutaneously daily for five days with conventional care or conventional treatment alone. Efficacy outcome measures were assessed at baseline, one month, and after six months of treatment included Barthel Index (BI), National Institute of Health Stroke Scale, and modified Rankin Scale. Results. One patient in G-CSF therapy arm died due to raised intracranial pressure. No severe adverse effects were seen in rest of patients receiving G-CSF therapy arm or control arm. No statistically significant difference between intervention and control was observed in any of the scores though a trend of higher improvement of BI score is seen in the intervention group. Conclusion. Although this study did not have power to examine efficacy, it provides preliminary evidence of potential safety, feasibility, and tolerability of G-CSF therapy. Further studies need to be done on a large sample to confirm the results.

Are therapeutic stem cells justified in bilateral multicystic kidney disease? A review of literature with insights into the embryology

Aim was to describe the challenges faced in the management of bilateral multicystic kidney disease (MCKD). A case of antenatally detected bilateral polycystic disease was referred at 28xa0weeks of gestation. The patient was advised to continue pregnancy till term and be in regular follow-up. Postnatally, the male baby passed urine in normal stream and was diagnosed as bilateral multicystic kidney disease on ultrasonography. He developed symptoms of renal failure. The baby was operated with right pyeloplasty and left pyelostomy, as the left ureter was atretic. The histopathology was consistent with bilateral multicystic kidney disease. Postoperatively, the baby was stable with intermittent episodes of metabolic acidosis that were managed medically and with peritoneal dialysis. Autologous stem cells were injected at the age of 1xa0year into the aorta at the level of the renal arteries clamping the aorta below. Repeat biopsy at time of stem cell injection showed 5/10 glomeruli showing global sclerosis on right side and 5/15 glomeruli showing global sclerosis on left side. The only improvement seen was in decreased doses of medicines to keep the child metabolically stable. The baby kept struggling but succumbed at the age of 17xa0months and 15xa0days. Post mortem bilateral renal biopsies demonstrated presence of primitive renal tubules and blastemal cells that were not demonstrated earlier. Survival for few months in bilateral multicystic kidney disease is thus possible with adequate treatment, the novel use of stem cells in these cases may prove beneficial in future though it is too early to comment further.

Colony-stimulating activity of fetal liver cells: synergistic role of stem cell factor in bone marrow recovery from aplastic anemia

Previously, we and others have shown that fetal liver infusion (FLI) leads to autologous hematopoietic improvement in 40-54% of patients with aplastic anemia. However, whether this recovery was spontaneous or the effect of the infused liver cells was not clear. To dissect the role of FLI in autologous hematopoietic recovery, the colony-supporting potential of fetal liver-conditioned medium (FLCM) was evaluated in bone marrow (BM) cells of normal adult and aplastic anemia patients. In both cases, each sample of FLCM supported the growth of colony-forming cells in semi solid culture medium. The FLCM was assayed for the presence of four principal colony-stimulating cytokines, namely stem cell factor (SCF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and erythropoietin (Epo). While GM-CSF, IL-3, and Epo were present in insignificant amounts or were altogether absent, 50-635 pg/ml of SCF was found in 8 of the 13 FLCM samples tested. Preliminary results of bioneutralization assay indicated the possible role of SCF, secreted by the FL cells, in colony-supporting activity of aplastic anemia and normal BM cells. Overall, our in vitro study implicates the paracrine role of infused FL cells in regenerating autologous hematopoiesis in aplastic anemia patients.