Short and long-term safety of lenograstim administration in healthy peripheral haematopoietic progenitor cell donors: a single centre experience.

Healthy donors (HDs) who were mobilized using lenograstim (LENO) and who were undergoing peripheral haematopoietic progenitor cell collection with apheresis (HPC-A) were enrolled in a surveillance protocol. In all, 184 HDs have been assessed with a median follow-up of 62 months (range 2-155). HDs received LENO at a median dose of 10 microg/kg (range 5-15). Bone pain was reported as the most frequent short-term adverse event (71.2%). Other commonly observed short-term symptoms included fatigue (19.0%), fever (5.4%), headache (27.7%), nausea (12.0%) and insomnia (22.3%). Spleen size increased in 4.3% of the donors. No vascular disorders or cardiac disease occurred. Long-term follow-up included monitoring of adverse events, neoplastic disease or other pathologies. Transit ischaemic attack occurred in one donor (39 months post-donation). One autoimmune event was reported at 28 months post-recombinant human granulocyte (rhG)-CSF (ankylosing spondylitis); one donor with a history of chronic obstructive pulmonary disease developed secondary polyglobulia (50 months post-rhG-CSF). One donor was diagnosed with lung cancer at 19 months post-donation. No haematological disease was observed. In conclusion, the short-term safety appears to be verified, whereas, although the study identified no increased risks of malignancy among HDs who received rhG-CSF, long-term safety requires more complete data sets, especially a longer follow-up and a larger number of HDs.

Fungal infections in recipients of hematopoietic stem cell transplants: results of the SEIFEM B-2004 study--Sorveglianza Epidemiologica Infezioni Fungine Nelle Emopatie Maligne.

BACKGROUND: The purpose of our study was to evaluate the incidence and outcome of invasive fungal infection (IFI) among patients who underwent autologous or allogeneic hematopoietic stem cell transplantation (HSCT) at 11 Italian transplantation centers. METHODS: This cohort-retrospective study, conducted during 1999-2003, involved HSCT patients admitted to 11 tertiary care centers or university hospitals in Italy, who developed IFIs (proven or probable). RESULTS: Among 3228 patients who underwent HSCT (1249 allogeneic HSCT recipients and 1979 autologous HSCT recipients), IFI occurred in 121 patients (overall incidence, 3.7%). Ninety-one episodes (2.8% of all patients) were due to molds, and 30 (0.9%) were due to yeasts. Ninety-eight episodes (7.8%) occurred among the 1249 allogeneic HSCT recipients, and 23 (1.2%) occurred among the 1979 autologous HSCT recipients. The most frequent etiological agents were Aspergillus species (86 episodes) and Candida species (30 episodes). The overall mortality rate was 5.7% among allogeneic HSCT recipients and 0.4% among autologous HSCT recipients, whereas the attributable mortality rate registered in our population was 65.3% (72.4% for allogeneic HSCT recipients and 34.7% for autologous HSCT recipients). Etiology influenced the patients' outcomes: the attributable mortality rate for aspergillosis was 72.1% (77.2% and 14.3% for allogeneic and autologous HSCT recipients, respectively), and the rate for Candida IFI was 50% (57.1% and 43.8% for allogeneic and autologous HSCT recipients, respectively). CONCLUSIONS: IFI represents a common complication for allogeneic HSCT recipients. Aspergillus species is the most frequently detected agent in these patients, and aspergillosis is characterized by a high mortality rate. Conversely, autologous HSCT recipients rarely develop aspergillosis, and the attributable mortality rate is markedly lower. Candidemia was observed less often than aspergillosis among both allogeneic and autologous HSCT recipients; furthermore, there was no difference in either the incidence of or the attributable mortality rate for candidemia among recipients of the 2 transplant types.

Harvesting peripheral blood progenitor cells from healthy donors with a short course of recombinant human granulocyte-colony-stimulating factor.

A short-course administration of non-glycosylated granulocyte-colony-stimulating factor (G-CSF) was investigated in 68 healthy donors (HDs) in order to collect > or = 4 x 10(6) CD34+ cells per kilogram of recipient's body weight. G-CSF was given at 10 microg/kg per day administered in two divided doses for 3 days. Leukapheresis was scheduled on day 4, 12 h after the last dose of G-CSF. A median of 35.6 circulating CD34+ cells microL(-1) (range, 3.1-185) was found on the day of leukapheresis. This allowed a median collection of CD34+ cells of 4.2 x 10(6) per kilogram of recipient's weight (range, 1.0-17.4). One single procedure was sufficient to reach the target level of CD34+ cells in 36 (53%) of 68 donors; significant correlations were found between the number of CD34+ cells collected on day 4 and the patient's sex, body-weight and volume of blood processed. A retrospective analysis was made with a historical group of HDs collected on day 5. The day 5 schedule allowed a more consistent achievement of the target cell dose with one leukapheresis (P = 0.005) and resulted in the initial collection of a significantly larger number of CD34+ cells (P = 0.006).

Distribution of potentially pathogenic bacteria as free living and plankton associated in a marine coastal zone.

AIMS: To determine the abundance of faecal and nonfaecal bacteria related to human and animal health, as free living or associated with small (>64 microm) and large (>200 microm) plankton, samples were collected monthly from the coastal zone at Messina (Italy). METHODS AND RESULTS: Different enrichment and selective cultural methods were used to determine the abundance of bacteria in sea water and plankton. The bacteria were more frequently isolated from water and large plankton than from small plankton. Vibrio and Aeromonas spp. showed different distribution patterns in water and plankton. Faecal indicators were always present in water and the large size class plankton samples. Enterococci associated with large plankton were more abundant than E. coli in the winter. Vibrio species distributions were different in water and plankton samples. Among arcobacters only A. butzleri was isolated from water and plankton samples. Campylobacter spp. was always absent in small plankton and more frequent in large plankton than in water. CONCLUSIONS: The colonization of zooplankton by potentially pathogenic bacteria is a widespread phenomenon. SIGNIFICANCE AND IMPACT OF THE STUDY: The presence of potentially pathogenic bacteria in sea water and associated with plankton can have ecological and epidemiological implications.

Systemic aspergillosis in a patient with non-Hodgkin's lymphoma developing acute graft-versus-host disease after autologous peripheral blood stem cell transplantation.

Graft-versus-host disease (GVHD) is rare in the autologous setting. We describe a non-Hodgkin's lymphoma case developing acute GVHD after autologous peripheral blood stem cell transplantation following several lines of chemotherapy inclusive of fludarabine. At day +33, he complained of fever, diffused erythematous papulosis with ulceration of skin lesions. A punch biopsy indicated a grade III GVHD. A dose escalation of corticosteroids, cyclosporin-A and photoapheresis induced a transient response. He developed positivity to CMV and systemic aspergillosis. He died at day +185 in haematological complete remission, despite infection-oriented treatment. In spite of the use of prophylactic immunosuppressive drugs, between 50% and 70% of patients given HLA-identical marrow graft develop acute graft-versus-host disease (GVHD) that, in turn, significantly increases the risk of transplant-related mortality. Autologous BMT has been shown to be an effective procedure in several malignancies, persistently becoming a first-line choice in treating patients affected with lymphoproliferative disorders, specially non-Hodgkin's lymphoma (NHL). Although GVHD is a very rare event in the autologous setting (AuGVHD), a consistent number of reports dealing with GVHD-like phenomena has emerged, especially in breast cancer patients. More often, AuGVHD has been induced by the use of immunosuppressive agents, such as cyclosporin-A (CSA), in attempt to evoke a graft-versus-tumor (GVT) effect. However, AuGVHD is mild and self-limited phenomenon. We report the case of a NHL patient who developed unresponsive GVHD after autologous peripheral blood stem cell transplantation (PBSCT). Because of the immunosuppressive therapies, he developed systemic aspergillosis. He died in haematological complete remission despite infection-oriented treatment.

Infectious complications in breast cancer patients undergoing peripheral blood stem cell transplantation: a single center retrospective analysis towards outpatient strategy.

Infectious complications were retrospectively analyzed in 129 transplants, performed in 90 patients, to identify characteristics that qualify breast cancer patients for outpatient-based PBSCT. Thirty-one cases (24%) did not develop fever. Of the remaining 98 cases, 84.7% developed fever during severe neutropenia. On univariate analysis, disease stages II-III, first PBSCT, mucositis grades II-IV and the use of two alkylators were associated with a higher risk of fever development. The latter two factors also affected fever occurrence on multivariate analysis. A longer median time to fever onset was observed in patients conditioned with single as compared to double alkylating agent-containing regimens (respectively 8th vs 6th day, P < 0.00001). As compared with metastatic breast cancer (MBC), high risk breast cancer showed a 2.3-fold increased risk of developing early fever during neutropenia (CI 2.3-3.8), remaining the only variable still significant on multivariate analysis (P = 0.0039). Combination antibiotic therapy was equivalent to single agent therapy. Patients suffering from microbiologically documented fever were at higher risk of undergoing second-line antibiotic therapy. In conclusion, MBC patients treated with a conditioning regimen containing only one alkylating agent and adequate prophylaxis for mucositis may qualify for outpatient-based PBSCT on the basis of a lower risk of infection.

In vitro improvement of chlorambucil-induced cytotoxicity by deflazacort and 6-methylprednisolone in B-cell chronic lymphocytic leukaemia.

We examined whether CLL cell chemosensitivity to in vitro exposure to chlorambucil (CLB) might be improved by the presence of deflazacort (DFZ) in comparison to 6-methylprednisolone (PDN). The PDN lethal dose (LD)50 values were low in 5 samples, intermediate in 4 and high in 7. Low, intermediate and high DFZ-LD50 values were detected in 3, 2 and 11 samples, respectively. The CBL-LD50 mean values were significantly reduced at all PDN and at the 4 highest DFZ concentrations. However, a dose-response effect was seen only in the DFZ group. Both CLB-DFZ and CLB-PDN interactions were analysed in 16 samples at 25 different dose-combinations, resulting in 400 comparisons between expected and observed leukaemic cell survival (LCS) values for each group. In particular, 45.75% and 40% dose combinations were synergistic in CLB-DFZ and CLB-PDN groups, respectively. A relatively higher number of antagonistic interactions were observed among CLB-PDN dose combinations, while analogous number of additive interactions were detected. At concentrations of CLB x1 microgram/ml the phenomenon of synergism, regardless of the steroid concentration, did occur more frequently. On the other hand, a more elevated number of antagonistic interactions were counted at CLB 100 micrograms/ ml. In conclusion, both DFZ and PDN synergize in vitro with CLB, especially at low concentrations of the alkylating agent.

Mobilization and collection of PBSC in healthy donors: a retrospective analysis of the Italian Bone Marrow Transplantation Group (GITMO).

BACKGROUND AND OBJECTIVE: The number of allogeneic transplants of peripheral blood stem cells (PBSC) is rapidly increasing. Collection of PBSC in healthy subjects currently implies the administration of G-CSF or GM-CSF and, of course, the use of apheretic devices. These procedures involve potential risks, in particular the risk of leukemia secondary to growth-factor treatment. To evaluate the current practice of PBSC mobilization and collection, and initially assess the short-term side effects and efficiency of procedures, the GITMO (Gruppo Italiano Trapianti di Midollo Osseo) promoted a retrospective cooperative study among the Italian centers. METHODS: Seventy-six healthy individuals donating to their HLA-identical or partially matched sibling recipients in seven Italian centers form the basis of the present analysis. The data were retrospectively collected by proper forms, pooled and analyzed by means of a commercially available statistical soft package. RESULTS: All donors received G-CSF as mobilizing agent with different schedules according to each single center policy. A median of 2.5 (range 1-4) aphereses per donor were run. The most frequent side effect was bone pain. In no case did the medium term follow-up reveal subjective complaints or laboratory modifications. After G-CSF mobilization, WBC and lymphocytes counts increased to a maximum of (mean +/- SD) 48.1 +/- 15.6 x 10(9)/L and 4.2 +/- 1.5 x 10(9)/L, respectively. The peak was reached on day 5 in both cases. Platelets decreased after the apheretic procedures, reaching a minimum of (mean +/- SD) 77 +/- 26 x 10(9)/L on day 8 and returning to normal values on day 11. Overall, the apheretic collection yielded (mean +/- SD) 18.6 +/- 19.2 x 10(8)/kg donor body weight MNC; 10.4 +/- 5.7 x 10(6)/kg CD34+ cells; 90.6 +/- 75.9 x 10(4)/kg CFU-GM and 4.3 +/- 1.8 x 10(8)/kg CD3+ cells. The target dose of 4 x 10(6)/kg CD34+ cells was harvested in 51.3% donors after a single apheresis, in 85.5% after the second, and in nearly 100% after a maximum of 3 aphereses. INTERPRETATION AND CONCLUSIONS: These data demonstrate that collection of adequate numbers of circulating progenitors is feasible and well tolerated in healthy donors. However, only careful monitoring of donors and international cooperation will help to definitively assess the long-term safety of G-CSF for mobilization of PBSC.

Two consecutive courses of rh-G-CSF-mobilized peripheral blood stem cells for primary marrow alloengraftment failure: case report.

We describe herein a case of bone marrow failure in a 53-year-old patient affected by Ph1-positive chronic myeloid leukemia who received an HLA-identical AB0-mismatched bone marrow transplant from a 56-year-old sibling donor. Hematopoietic recovery after marrow failure was obtained following two consecutive courses of rh-G-CSF-mobilized peripheral blood stem cell infusions. No potential risk factors associated with graft failure, excluding recipient and donor age, were documented, whereas a relatively high number of progenitor cells were necessary to overcome the host-versus-graft barrier in our patient. Therefore we suggest that growth factor-stimulated peripheral blood should be considered as the first choice for allogeneic stem cells in order to avoid primary graft failure with donors over 50 years of age.

Fractionated infusions of cryopreserved stem cells may prevent DMSO-induced major cardiac complications in graft recipients.

The amount of transfused dimethyl sulfoxide (DMSO) is indicated as the major cause of the cryoprotectant-related toxicity in autologous stem cell recipients, with a high incidence of major cardiac side effects. In this study we tried to discover whether fractionated infusion of the total graft volume could prevent the DMSO-related major cardiovascular side effects. We conclude that continuous cardiac monitoring during and after fractionated infusions of DMSO-containing graft documented no major arrhythmias, with only seven episodes of asymptomatic sinus bradycardia.

[Magnetic resonance aspects of the bone marrow in aplastic anemia at the onset and in the follow-up after transplant]. / Aspetti con risonanza magnetica del midollo osseo nell'anemia aplastica all'esordio e nel follow-up dopo trapianto.

Aplastic anemia is a rare hematologic disorder characterized by hypocellular fatty marrow. Aplastic anemia is diagnosed on the basis of laboratory tests and bone marrow biopsy findings. Biopsy is of fundamental importance for bone marrow assessment, though not representative of the rest of the marrow. Thanks to its exclusive capabilities in the direct visualization of bone marrow, MRI is a noninvasive and relatively rapid method for bone marrow study. The authors report their experience in 3 aplastic anemia patients examined also with MRI at presentation and after marrow transplantation. The dorsolumbar spine was studied with sagittal SE T1-weighted and STIR sequences, while pelvic bones were investigated only with SE T1-weighted sequences in all patients. Two of them were also examined with sagittal scans of the dorsolumbar spine using the chemical shift fat suppression technique. In all three patients, SE T1-weighted images at presentation showed fatty bone marrow infiltration, also confirmed on fat suppression images, and, after transplantation, progressive bone marrow repopulation, with the typical "band" pattern in vertebral marrow. Although MR specificity remains low in the demonstration of bone marrow disorders, the authors believe it to be a useful tool, after accurate clinical and laboratory exams, not only in the diagnosis but also and especially in the follow-up of these disorders.