Sperm cryopreservation before testicular cancer treatment and its subsequent utilization for the treatment of infertility.

AIMS: In this study we report our results with storage of cryopreserved semen intended for preservation and subsequent infertility treatment in men with testicular cancer during the last 18 years. METHODS: Cryopreserved semen of 523 men with testicular cancer was collected between October 1995 and the end of December 2012. Semen of 34 men (6.5%) was used for fertilization of their partners. They underwent 57 treatment cycles with cryopreserved, fresh, and/or donor sperm. RESULTS: A total of 557 men have decided to freeze their semen before cancer treatment. Azoospermia was diagnosed in 34 men (6.1%), and semen was cryopreserved in 532 patients. Seminoma was diagnosed in 283 men (54.1%) and nonseminomatous germ cell tumors in 240 men (45.9%). 34 patients who returned for infertility treatment underwent 46 treatment cycles with cryopreserved sperm. Totally 16 pregnancies were achieved, that is, 34.8% pregnancy rate. CONCLUSION: The testicular cancer survivors have a good chance of fathering a child by using sperm cryopreserved prior to the oncology treatment, even when it contains only limited number of spermatozoa.

Efficacious but insidious: a retrospective analysis of fludarabine-induced myelotoxicity using long-term culture-initiating cells in 100 follicular lymphoma patients.

OBJECTIVE: Fludarabine has been recognized as effective treatment in patients with follicular lymphoma (FL), but can induce myelotoxicity of unknown mechanism. MATERIALS AND METHODS: Myelotoxicity was assessed by cultivation of two types of hematopoietic progenitor cells: colony-forming units granulocyte-macrophage (CFU-GM) and long-term culture-initiating cells (LTC-IC). Pretreatment amounts of CFU-GM and LTC-IC were correlated to age, gender, stage of disease, bone marrow involvement, and previous therapy. Posttreatment comparison of CFU-GM and LTC-IC was performed after different regimens of chemotherapy: fludarabine-based (FND +/- R), procarbazine-based (COPP +/- R), and CHOP(cyclophosphamide, doxorubicin, vincristine, prednisone) +/- R(Rituximab). RESULTS: One-hundred patients (median age 55 years; 21 patients relapsed) treated for FL were analyzed. The total number of progenitor hematopoietic cells in both types of cultures varied in wide ranges; for LTC-IC between 0 and 874 cells/mL with a median of 77.71 cells/mL and for CFU-GM between 0 and 531 x 10(2) cells/mL with a median of 30.58 x 10(2) cells/mL. Bone marrow involvement, gender, stage of disease, or previous therapy had no influence on LTC-IC and CFU-GM counts. We identified an increase in LTC-IC, but not CFU-GM, associated with age (p = 0.01). Median figures for CFU-GM and LTC-IC were found to be significantly lower after FND +/- R and COPP +/- R than after CHOP +/- R therapy, compared to baseline values (p < 0.01). CONCLUSIONS: Fludarabine and procarbazine have a dramatic influence, especially on the most immature hematopoietic cells, mirrored in reduced numbers of LTC-IC. This finding is consistent with clinical observations (poor mobilization after fludarabine) and offers an insight into the mechanism of fludarabine-induced myelotoxicity.

Three-, 6-, and 12-month results of autologous transplantation of mononuclear bone marrow cells in patients with acute myocardial infarction.

BACKGROUND: There are only few data on long-term effectiveness of the stem cell therapy. AIM: We studied the time course of global and regional left ventricular function in patients with acute myocardial infarction within 1 year after the autologous mononuclear bone marrow cell transplantation. METHODS: Sixty patients with a first acute myocardial infarction, who had been randomized into 3 groups, completed a 12-month protocol. Two groups were intracoronarily given bone marrow cells in either higher (10(8) cells, HD group, n=20) or lower (10(7) cells, LD group, n=20) doses. Twenty patients without cell transplantation served as a control (C) group. Doppler tissue imaging and the gated technetium-99m sestamibi single photon emission computed tomography were performed before cell transplantation and at 3, 6, and 12 months later. RESULTS: The baseline peak systolic velocities of longitudinal contraction of the infarcted wall (S(infarct)) of 5.2 cm/s, 4.6 cm/s, and 4.4 cm/s in C, LD, and HD groups increased by 0.0 cm/s, 0.3 cm/s (p=NS vs. C group), and by 0.7 cm/s (p<0.05 vs. C group), respectively, at 3 months. At 12 months, however, the corresponding changes from baseline values of 0.1 cm/s, 0.2 cm/s, and 0.6 cm/s did not differ significantly (all p=NS). In contrast, the post-transplant improvements in the left ventricular ejection fraction by 6%, 7%, and 7% at months 3, 6, and 12, respectively, were preserved in HD group patients during the whole 12-month follow-up and remained significantly better as compared to controls. CONCLUSIONS: In our study, the autologous mononuclear bone marrow cell transplantation provided sustained improvement in global left ventricular systolic function in patients with acute myocardial infarction. However, when evaluating regional systolic function of the infarcted wall, the short-term benefit was partially lost during the 12-month follow-up.

Autologous transplantation of mononuclear bone marrow cells in patients with acute myocardial infarction: the effect of the dose of transplanted cells on myocardial function.

BACKGROUND: Despite the reports on successful treatment of acute myocardial infarction using autologous mononuclear bone marrow cell transplantation, many unresolved questions still remain. We studied the impact of the dose of transplanted cells on myocardial function and perfusion. METHODS: Sixty-six patients with a first acute myocardial infarction were randomized into 3 groups. Two groups were intracoronarily given mononuclear bone marrow cells in either higher (10(8) cells, higher cell dose [HD] group, n = 22) or lower (10(7) cells, lower cell dose [LD] group, n = 22) doses. Twenty-two patients without cell transplantation served as a control (C) group. RESULTS: At 3 months of follow-up, the baseline peak systolic velocities of longitudinal contraction of the infarcted wall of 5.2, 4.5, and 4.3 cm/s in C, LD, and HD groups increased by 0.0, 0.5 (P < .05 vs C group), and 0.9 cm/s (P < .05 vs LD group, P < .01 vs C group), respectively, as demonstrated by Doppler tissue imaging. Baseline left ventricular ejection fractions of 42%, 42%, and 41% in C, LD, and HD groups increased by 2%, 3%, and by 5% (P < .05 vs group C), respectively, as assessed by the gated technetium Tc 99m sestamibi single photon emission computed tomography. CONCLUSIONS: Mononuclear bone marrow cell transplantation improves regional myocardial function of the infarcted wall in a dose-dependent manner.

Treatment of chronic myeloid leukemia with autologous transplantation using peripheral blood stem cells or bone marrow cultured in IL-2 followed by IL-2, GM-CSF, and IFN-alpha administration.

Interleukin-2 (IL-2) is able to generate nonspecific cytotoxic effectors from hematopoietic precursors. We evaluated the feasibility and efficacy of chronic myeloid leukemia (CML) treatment with autologous hematopoietic stem cell transplantation (HSCT) using grafts cultured in IL-2 followed by immunotherapy with IL-2, granulocyte-macrophage colony-stimulating factor (GM-CSF), and interferon (IFN)-alpha. Eight patients with CML were enrolled: five in an accelerated phase and three in a chronic phase. They received peripheral blood stem cells (PBSC) or bone marrow (BM) cultured in a medium containing IL-2 for 24 h. A median of 1.29 x 10(6) CD34+ cells/kg were infused after conditioning with busulfan (12 16 mg/kg) in PBSC recipients. BM was infused without prior myeloablative therapy. The engraftment occurred with a median of 15 d. Engraftment failure developed in one patient. The transplantation was followed by a 1-mo regimen of IL-2 (0.5 x 10(6) IU/m(2) daily) and GM-CSF, and 6 mo of IFN-alpha. One complete and one transient minor cytogenetic remission were observed. At 24 mo after transplantation, two patients had died of progressive disease and one of infection. Five patients had stable disease in the chronic phase. Autologous transplantation using IL-2-activated graft is feasible and the subsequent IL-2, GM-CSF, and IFN-alpha administration has acceptable toxicity. However, no benefits in comparison with conventional autologous transplantation for CML were identified in our study.