CD3+ graft cell count influence on chronic GVHD in haploidentical allogeneic transplantation using post-transplant cyclophosphamide.

The effects of graft or donor characteristics in haploidentical hematopoietic cell transplantation (HCT) using post-transplant cyclophosphamide (PT-Cy) are largely unknown. In this multicenter retrospective study we analyzed the correlations between graft cell composition (CD34+, CD3+) and donor features on transplant outcomes in 234 patients who underwent HCT between 2010 and 2016. On multivariate analysis, the use of peripheral blood stem cells (PBSC) was associated with an increased incidence of grade 2-4 acute GVHD [HR 1.94, 95% confidence Interval (CI) = 1.01-3.98, p = 0.05]. An elevated CD3+ graft content was associated with an increased incidence of all-grade chronic GVHD [HR 1.36 (95% CI = 1.06-1.74), p = 0.01]. This effect was confirmed only for the PBSC graft group. A higher CD34+ graft content had a protective role on non-relapse mortality [HR 0.78 (95% CI = 0.62-0.96), p = 0.02] but this was confirmed only for the bone marrow (BM)-derived graft cohort. Donor characteristics did not influence any outcomes. GVHD prophylaxis should be modulated accordingly to CD3+ graft content, especially when a PBSC graft is used. These results need further validation in prospective trials.

Allogeneic stem cell transplantation and subsequent treatments as a comprehensive strategy for long-term survival of multiple myeloma patients.

We evaluated 71 patients treated with allogeneic hematopoietic cell transplantation (allo-HCT) for multiple myeloma (MM). Forty-three patients (61%) received allo-HCT after the first line of therapy. Fifty-eight patients (82%) had chemosensitive disease at the time of allo-HCT. A HLA-matched related or unrelated donor was available for 68 patients (96%). Non-myeloablative or reduced-intensity conditioning regimen and peripheral blood hematopoietic cells as a graft source were used in most patients. The cumulative incidence of grade II-IV acute GVHD at day +100 and chronic GVHD at 5 years was 13% (95% CI 7-23%) and 35% (95% CI 24-46), respectively. Non-relapse mortality and relapse/progression incidence at 5 years were 12% (95% CI 5-23) and 65% (95% CI 49-76), respectively. With a median follow-up in survivors of 100 months (range 16-186), the 5-year PFS and OS were 39% (95% CI 27-52) and 60% (95% CI 55-77), respectively. On multivariate analysis: age >55 years was associated with both a reduced PFS (RR 2.11, 95% CI 1.15-3.87) and OS (RR 5.53, 95% CI 2.22-13.76); chemorefractory disease at allo-HCT was associated with both reduced PFS (RR 3.09, 95% CI 1.37-7.00) and OS (RR 3.19, 95% CI 1.23-8.22). At relapse, 24 patients (56%) received bortezomib, 28 (65%) lenalidomide, 11 (26%) pomalidomide, 16 (37%) donor lymphocytes infusion as part of salvage therapy after allo-HCT relapse. Median PFS from time of salvage treatment was 7 months (range 0-113 months) for bortezomib-based therapy, 14 months (range 0-79 months) for lenalidomide and 10 months (range 1-28) for pomalidomide. Allo-HCT is a feasible and effective strategy in selected patients with MM and could be an effective platform for subsequent therapies.

An assessment of the operating characteristics of Coulter Counter Model S-Plus STKR.

BACKGROUND AND METHODS: The operating performance of the Coulter Counter S Plus STKR was evaluated in two hospital laboratories in Rome and in Florence. Experimental design conformed to both the ICSH and NCCLS Standards for the evaluation of hematologic analyzers, and to the ECCLS guidelines for the multicenter evaluation of analyzers in clinical chemistry. RESULTS AND CONCLUSIONS: Cell counts in K3 EDTA were unchanged over 6 hours at room temperature and 72 hours at 4 degrees C, while MCV, MPV and leukocyte differentials were far less stable. Carry over, precision and linearity met the manufacturer's specifications, while a satisfactory relative accuracy was demonstrated by determining reference values on an adult reference group and by comparing the instrument with the previous model S Plus IV D. The accuracy of the leukocyte differentials was evaluated by the microscope reference method, and our results seemed to validate the hypotheses that the STKR model counts: i) eosinophils, basophils and banded neutrophils among GR; ii) variant lymphocytes among LY, and iii) various abnormal cells among mononuclear cells. However, in spite of this statistical significance, some difficulties in correctly classifying the mononuclear population were demonstrated.

Analysis of leucocyte populations with the Coulter S-Plus STKR as a screening tool for haematological abnormalities.

In two institutions at Rome and Florence we evaluated the clinical sensitivity of two Coulter STKR systems using the NCCLS standard H20-T for leucocyte differential count in a patient population with high prevalence of haematologic abnormalities. Reference ranges of normal leucocytes were obtained on 278 adult subjects. On a population of 455 patient specimens, 200 specimens (44%) were flagged by the STKR because of a distributional abnormality, and 122 (27%) because of a morphological abnormality. Percentage of subtotal agreements between the STKR and the reference manual differential count was 85.4%, with 67.5% full and 20.9% partial agreements. Eight specimens that showed a morphological abnormality with the reference manual differential count were classified as normal by the STKR, with a false normal rate of 6.6%. Analysis of the STKR performance for morphological abnormalities showed acceptable sensitivity (82.0%) and rather low specificity (71.5%), low predictive value of positive results (51.3), high predictive value of negative results (91.5%) and efficiency of 74.3%. The main problems of the STKR differential count were a high rate of false monocyte count, and the misidentification of eosinophilias and low-concentration abnormal cells.

[Changes in the serum protein picture in viral hepatitis. II. Evaluation of the proteins in the acute phase]. / Modificazioni del quadro sieroproteico nell'epatite virale. II. Valutazione delle proteine della fase acuta.

A few of the best known acute phase reactants have been followed in 30 patients suffering from acute viral hepatitis during the first four weeks of illness. Increased levels of alpha-1 antitrypsin and prevailing low levels of haptoglobin were the main findings, while the other proteins showed only little changes. As a whole the determination of acute phase reactants does not seem of any particular significance in viral hepatitis.

[Changes in the serum protein picture in viral hepatitis. III. Evaluation of immunoglobulins]. / Modificazioni del quadro sieroproteico nell'epatite virale. III. Valutazione delle immunoglobuline.

Serum IgG, IgA and IgM were determined sequentially during the first four weeks of illness in 30 patients suffering from acute viral hepatitis. Initially increased levels of IgM, and to a lower extent of IgG were the most characteristic findings. Two patients showed increased levels of IgA. The determination of immunoglobulins is not contributory to the diagnosis of viral hepatitis, though it may have a significant value in detecting the activity of the disease.