Rapid hematopoietic engraftment following fractionated TBI conditioning and transplantation with CD34(+) enriched hematopoietic progenitor cells from partially mismatched related donors.

Nineteen adult patients with poor-risk hematologic malignancy received T cell-depleted (TCD) hematopoietic progenitor cell (HPC) transplant from partially mismatched related donors (PMRD). The preparative regimen (FITFA) included fractionated TBI, thiotepa, fludarabine, and horse (n = 3) or rabbit (n = 16) anti-thymocyte anti-sera (ATG). GVHD prophylaxis consisted of TCD by positive/negative selection using the Isolex 300i system and pre-transplant ATG with no post-transplant immunosuppression. The mean number (+/-s.d.) of transplanted CD34(+) and CD3(+) cells were 8.9 x 10(6)/kg +/-4.3 (range 2.6-19.3) and 1.4 x 10(4)/kg +/-1.2 (range 0.3-4.6) respectively. Seventeen patients evaluable for neutrophil engraftment achieved an ANC >0.5 x 10(9)/l at a median of 12 days (range 9-27), with evidence of full donor chimerism. Thirteen patients died of the following causes: relapse (n = 6), infections (n = 5), interstitial pneumonia (n = 1), and unknown causes (n = 1) None of the recipients of rabbit ATG required therapy for acute or chronic GVHD. Five patients are alive and disease-free at a median time of 303 days post transplant (range 100-660). The FITFA preparative regimen using fractionated TBI is well tolerated and is sufficiently immunosuppressive to allow rapid and stable donor origin hematopoietic engraftment without 'mega' doses of CD34(+) cells. Combination of stringent ex vivo TCD and pre-transplant ATG is effective GVHD prophylaxis.

Effects of megakaryocyte growth and development factor on platelet production, platelet life span, and platelet function in healthy human volunteers.

The effects of thrombopoietic stimulation on megakaryocytopoiesis, platelet production, and platelet viability and function were examined in normal volunteers randomized to receive single bolus subcutaneous injections of 3 microg/kg pegylated recombinant megakaryocyte growth and development factor (PEG-rHuMGDF) or placebo in a 3:1 ratio. PEG-rHuMGDF transiently doubled circulating platelet counts, from 237 +/- 41 x 10(3)/microL to 522 +/- 90 x 10(3)/microL (P <.0001), peaking on day 12. Baseline and day-12 samples showed no differences in responsiveness of platelets to adenosine diphosphate or thrombin receptor agonist peptide (P >.4 in all cases); expression of platelet ligand-induced binding sites or annexin V binding sites (P >.6 in both cases); or density of platelet TPO-receptors (P >.5). Platelet counts normalized by day 28. The life span of autologous (111)In-labeled platelets increased from 205 +/- 18 hours (baseline) to 226 +/- 22 hours (P <.01) on day 8. Platelet life span decreased from 226 +/- 22 hours (day 8) to 178 +/- 53 hours (P <.05) on day 18. The theoretical basis for senescent changes in mean platelet life span was illustrated by biomathematical modeling. Platelet turnover increased from 43.9 +/- 11.9 x 10(3) platelets/microL/d (baseline) to 101 +/- 27.6 x 10(3) platelets/microL/d (P =.0009), and marrow megakaryocyte mass expanded from 37.4 +/- 18.5 fL/kg to 62 +/- 17 x 10(10) fL/kg (P =. 015). Although PEG-rHuMGDF initially increased megakaryocyte volume and ploidy, subsequently ploidy showed a transient reciprocal decrease when the platelet counts exceeded placebo values. In healthy human volunteers PEG-rHuMGDF transiently increases megakaryocytopoiesis 2-fold. Additionally, peripheral platelets expand correspondingly and exhibit normal function and viability during the ensuing 10 days. The induced perturbation in steady state thrombopoiesis resolves by 4 weeks. (Blood. 2000;95:2514-2522)

Repair of inguinal hernia in the adult with Prolene mesh.

Three surgeons in the private practice of general surgery began to use Prolene (polypropylene) mesh in the treatment of all adult inguinal hernias in 1978. The reason for using this technique was to perform a truly tension-free repair to reduce the recurrence rate and produce less pain and disability postoperatively. The rational for using Prolene as the mesh material is discussed in relation with the other materials available. The technique is outlined in detail along with precautions to decrease the already low recurrence rate documented in this series. From 1978 through 1985, 745 repairs were analysed. The complication and recurrence rates were minimal, and the follow-up rate was 87 per cent. A plea is made not to report recurrence rates without follow-up rates. This technique is simple and effective and should be seriously considered in the treatment of hernias occurring in adults.