Prognostic factors and long-term outcome of autologous haematopoietic stem cell transplantation following a uniform-modified BEAM-conditioning regimen for patients with refractory or relapsed Hodgkin lymphoma: a single-center experience.

Despite the well-defined role of autologous haematopoietic stem cell transplantation (autoHCT) in the treatment of patients with relapsed or refractory Hodgkin lymphoma (HL), relapse remains the main cause of transplant failure. We retrospectively evaluated long-term outcome and prognostic factors affecting survival of 132 patients with refractory (n = 89) or relapsed HL (n = 43) treated with autoHCT following modified BEAM. With a median follow-up of 68 months, the 10-year overall survival (OS) and progression-free survival (PFS) were 76 and 66 %, respectively. The 10-year cumulative incidence of second malignancies was 7 %. In multivariate analysis, age ≥45 years, more than one salvage regimens and disease status at transplant worse than CR were factors predictive for poor OS. In relapsed HL, age at transplant, response duration (<12 vs. ≥12 months) and the number of salvage regimens were independent predictors for PFS. In the refractory setting, disease status at autoHCT and the number of salvage regimens impacted PFS. The number of risk factors was inversely correlated with PFS in both relapsed and refractory HL (p = 0.003 and <0.001, respectively). The median PFS for patients with >1 risk factor in the relapsed and refractory setting was 5 and 11 months, respectively, in comparison with the median PFS not reached for patients with 0-1 risk factor in both settings. We conclude that high proportion of patients with relapsed/refractory HL can be cured with autoHCT. However, the presence of two or more risk factors helps to identify poor prognosis patients who may benefit from novel treatment strategies.

Exercise capacity, arrhythmic risk profile, and pulmonary function is not influenced by intracoronary injection of bone marrow stem cells in patients with acute myocardial infarction.

OBJECTIVES: To evaluate influence of Bone Marrow Stem Cells (BMSC) intracoronary infusion on exercise capacity, pulmonary function, heart rate recovery and SAECG in patients with AMI of anterior wall, compared to control group--from baseline in the acute phase during 12 months follow up. METHODS: Forty five patients were randomized 2:1 to BMSC group (n = 31 pts) or to control group (n = 14 pts). BMSC were administered into infarct related artery (IRA) at 4-6 day after primary PCI. Patients were followed up with cardiopulmonary exercise testing. The QRS duration, QT and QTc interval were measured and signal averaged ECGs (SAECG) were performed to evaluate late potentials. RESULTS: There were no significant differences between both groups neither at peak VO(2) (190.7 ± 7.4 at baseline; 24.2 ± 5.2 at 6 months; 22.2 ± 7.4 ml/kg/min at 12 months vs 18.4 ± 8.2 at baseline; 22.0 ± 7.2 at 6 months; 21.8 ± 6.2 ml/kg/min at 12 months; BMSC vs control group respectively; p = ns), nor VO(2) at anaerobic threshold, nor in VE/VCO(2) slope, RER, and systolic blood pressure at peak exercise at baseline and any time point of follow-up. There were no significant differences between groups concerning HR peak, HRR1 and HRR2 at any time point and also QRS, QT parameters, and SAEKG. There were no significant differences between both groups at any time point (baseline, 6 and 12 months) concerning FVC, FEV(1) and FVC/FEV(1) and % of their normal values. CONCLUSIONS: We did not find that BMSC therapy in patients with anterior wall myocardial infarction influences exercise capacity. We did not confirm it's potential proarrhythmogenic influence as assessed with SAECG and standard ECG analysis.

Influence of bone marrow stem cells on left ventricle perfusion and ejection fraction in patients with acute myocardial infarction of anterior wall: randomized clinical trial: Impact of bone marrow stem cell intracoronary infusion on improvement of microcirculation.

AIMS: Randomized trial to assess change in left ventricle ejection fraction (LVEF) and myocardial perfusion in patients with acute myocardial infarction (AMI) of anterior wall treated with bone marrow stem cells (BMSCs), compared with control group-from baseline in the acute phase up to 12 months of follow-up. METHODS AND RESULTS: Forty-five patients were randomized 2:1 to BMSC group (n= 31) or to control group (n = 14). Bone marrow stem cells were administered into infarct-related artery (IRA) at 4-6 day after primary PCI. Groups were followed up with Tc-99m-MIBI SPECT, radionuclide ventriculography (EF-RNV), echocardiography (ECHO), and spiroergometric stress test. Coronary angiography was repeated after 6 months. EF-RNV did not differ significantly in both groups, but trend towards increase in EF at 6 months and its maintenance after 12 months was noticed in the BMSC group. At rest study, perfusion index (PI) of region supplied with blood by IRA distal to its previous occlusion (PI-IRA) improved significantly in the BMSC group at 6 months: PI-IRA at 4-6 days vs. PI-IRA at 6 months (3.00 +/- 0.97 vs. 2.65 +/- 0.64; P = 0.017). At 12 months, PI-IRA at rest was 2.66 +/- 0.55; P = 0.07. The difference between BMSC and control groups at rest study in PI-IRA was not observed. At dipyridamole study (PI-dip), perfusion in the BMSC group was better compared with controls at 6 months (2.26 +/- 0.44 vs. 2.47 +/- 0.40; P = 0.033) and at 12 months (2.34 +/- 0.55 vs. 2.52 +/- 0.42; P = 0.014), also for region supplied with blood by IRA (PI-IRA-dip; at 6 months 2.63 +/- 0.77 vs. 3.06 +/- 0.46; P = 0.021 and at 12 months 2.71 +/- 0.63 vs. 3.15 +/- 0.51; P = 0.001). Results of LVEF, LVEDV, LVESV in ECHO and results of spiroergometric stress test did not differ significantly between groups. Major adverse cardiac events occurred more often in the control group (P = 0.027). CONCLUSION: In our study, BMSC intracoronary transplantation in patients with anterior AMI did not result in increase in EF. Slight improvement of myocardial perfusion was noticed in the BMSC group. This finding may indicate better microcirculation enhanced by BMSCs, but small number of patients allow for hypothesis rather than final statement.

[Suppressive effect of high-dose chemotherapy (HDC) on the clonal growth of grafted peripheral blood granulocyte progenitors is reduced 72 hours after completion of HDC]. / Hamujacy wplyw wysokodawkowej chemioterapii na wzrost klonalny przeszczepianych prekursorów granulocytarnych krwi jest redukowany po 72 godzinach od jej zakonczenia.

Hematopoietic stem cells (HSC) transplantations are usually performed 24-48 hours after the end od high-dose chemotherapy (HDC). It is possible, however, that at that time the transplanted HSC can be affected by the administered drugs. We report the results obtained in 30 patients (pts) with hematological malignancies (multiple myeloma - 14, Hodgkin's disease -6, non-Hodgkin's lymphomas -4, chronic myeloid leukemia -6) treated with HDC with peripheral blood stem cell transplantation (PBSCT). The following HDC regimens were applied: melphalan - 14, Dexa-BEAM (dexamethasone, BCNU, etoposide, cytarabine, melphalan) - 10 and BuCy2 (busulfan, cyclophosphamide) - 6. To evaluate the impact of HDC on the growth ability of less /14/ and more /7/ mature CFU-GM, sera were taken directly before cytoreductive chemotherapy, on the last day of HDC (0 day) and on days 1, 2, 3, 4 and 5 after the end of HDC. After melphalan, for CFU-GM/14/ the following results were received: days 0 - 54 +/- 9, 1 - 55 +/- 9, 2 - 68 +/- 12, 3 - 82 +/- 10, 4 - 95 +/- 8,5 - 100 +/- 8% and for CFU-GM/7/: days 0 - 60 +/- 11, 1 - 59 +/- 8, 2 - 72 +/- 11, 3 - 80 +/- 7, 4 - 90 +/- 9, 5 - 105 +/- 7%, determined as a percentage of those obtained before HDC (100%). After Dexa-BEAM, for CFU-GM/14/: days 0 - 45 +/- 13, 1 - 49 +/- 8, 2 - 59 +/- 12, 3 - 85 +/- 15, 4 - 96 +/- 9, 5 - 106 +/- 11%, and for CFU-GM/7/: 0 - 43 +/- 15, 1 - 50 +/- 9, 2 - 63 +/- 11, 3 - 89 +/- 11, 4 - 98 +/- 11, 5 - 110 +/- 8%. In case of BuCy2, for CFU-GM/14/: days 0 - 55 +/- 13, 1 - 67 +/- 7, 2 - 69 +/- 15, 3 - 85 +/- 10, 4 - 103 +/- 12, 5 - 108 +/- 7% and for CFU-GM/7/: days 0 - 50 +/- 12, 1 - 71 +/- 6, 2 - 76 +/- 16, 3 - 98 +/- 9, 4 - 105 +/- 11, 5 - 101 +/- 8%. In all pts PBSCT were infused 72 hours after HDC. The median time to reach granulocytes > 0.5 G/l and >1.0 G/l was 12 (8-17) and 13 (9-18) days, respectively. The recovery of platelets >20.0 G/l and >50. 0 G/l occured after 17 (9-48) and 25 (11-54) days, respectively. We conclude that the suppressive effect of the sera taken on days 0-2 on the CFU-GM growth depends on the HDC-regimen. We have also shown that third day after completion of HDC is the optimal time for the infusion of HSC. The time of hematological reconstituton is related in all investigated pts and independently on the HDC-program (p>0.05).