A novel type of metastatically spreading subcutaneous aspergillosis without epidermal lesions following allogeneic stem cell transplantation.

Systemic mycosis is among the most feared opportunistic infections in the immunocompromised host. Difficulty and delay in diagnosis and treatment often result in poor outcomes. In this communication a metastatically spreading form of subcutaneous aspergillosis developed in a patient with a history of allogeneic stem cell transplantation for relapsed Hodgkin's lymphoma. Strikingly, necrotizing cutaneous papules or ulcerating lesions were absent. Diagnosis was accomplished after excision of a clinically non-suggestive subcutaneous nodule. Despite prompt initiation of antimycotic therapy the outcome was fatal; dosage of conventional and liposomal amphotericin B was limited due to treatment-related toxicities. This case report describes a novel form of aspergillosis and underlines the need for an aggressive diagnostic approach in severely immunocompromised patients.

Massive extramedullary disease progression in a patient with stable multiple myeloma during G-CSF priming for peripheral blood progenitor mobilization.

High dose therapy followed by autologous peripheral blood progenitor cell (PBPC) transplantation has recently become an encouraging treatment option for younger patients with multiple myeloma (MM). The influence of the growth factors used for progenitor mobilization on myeloma cells is not known. We report on a patient suffering from IgG kappa myeloma who had been in stable, very good partial remission for seven months after standard therapy until PBPC mobilization with granulocyte-colony stimulating factor (G-CSF, Filgrastim) was initiated. Massive extramedullary disease progression occured coincidentally with the administration of G-CSF. The case suggest the possibility of myeloma stimulation by G-CSF during PBPC mobilization.

Dyshematopoiesis in de novo acute myeloid leukemia: cell biological features and prognostic significance.

Dyshematopoiesis was found in 44 (42.3%) of 104 cases of de novo acute myeloid leukemia (AML). Dyshematopoietic AML (dys-AML) and AML without hematopoietic dysplasia (non-dys-AML) were compared with regard to biological, hematological, immunophenotypic, and cytogenetic parameters as well as prognostic criteria. Median age of patients was 55 years in both groups. In dys-AML, the median leukocyte count (p = 0.04), peripheral blast (p = 0.02) and medullary blast cell count (p < 0.001) were significantly decreased, whereas the median platelet count (p - 0.04) was increased. Immunophenotyping demonstrated that leukemic blast cells in dys-AML more frequently expressed the adhesion molcules CD54 (p = 0.05) and CD58 (p = 0.08) than leukemic cells in non-dys-AML. Cytogenetically, we distinguished two karyotypic patterns, one group with a normal karyotype or prognostically favorable single chromosome aberrations ("P(0)-karyotype"), and another one with unfavorable single aberrations or complex aberrations ("P(1)-karyotype"). The incidence of these groups was not significantly different between dys-AML and non-dys-AML. Complete remission rate (CRR) after induction chemotherapy (p = 0.03) and overall survival time (OS; p = 0.03) were significantly lower in dys-AML. In addition, median disease free survival (DFS; p = n.s.) was inferior compared to non-dys-AML. In the dys-AML as well as in the non-dys-AML patient group, CRR, DFS, and OS were decreased in the P(1)-compared to the P(0)-subgroup. We conclude that dyshematopoietic AML is characterized by specific cell biological features and that hematopoietic and cytogenetic status represent complementary prognostic factors in de novo AML.

Large volume leukapheresis maximizes the progenitor cell yield for allogeneic peripheral blood progenitor donation.

We have investigated the efficiency and safety of large volume leukapheresis (LVL) for the collection of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood progenitor cells (PBPCs) from healthy donors. In six apheresis sessions in four healthy individuals on a COBE-BCT Spectra cell separator (median processed volume 3.5 X total blood volume, TBV, range 3.3-4.4 X TBV), harvested cells were collected sequentially into three single bags. The collection bags were changed after processing 33%, 66%, and 100% of the prospective apheresis volume, allowing analysis of PBPCs collected at different periods during one harvest. Mononuclear cells (MNCs), CD34+ cells, CD34+ subsets, and lymphocyte subsets were determined in each bag. Substantially more PBPCs were harvested than were in the circulation before G-CSF administration preceding LVL (median 171%, range 69-267%), reflecting progenitor release during the procedure. In donors 1 and 3, the CD34+ cell yields decreased in the third bag to 53% and 42% of that collected in the first bag, whereas the progenitor cell yields in donors 2 and 4 were stable or rose during the procedure, achieving in the third bag 157% and 105% of the number of CD34+ cells collected in the first bag. Minor changes were found in the subsets of CD34+ cells, lymphocytes, and monocytes collected at different periods during a single harvest. LVL was well tolerated. Reversible thombocytopenia developed in all cases. No late effects attributable to LVL or G-CSF were found in the 4 donors and 16 other healthy individuals who have undergone LVL in our institution. We conclude that LVL is safe and maximizes PBPC yields for allogeneic transplantation.

Long-term survival of recipients of allogeneic bone-marrow transplantation after mechanical ventilation.

To evaluate the prognostic significance of mechanical ventilation for outcome of intensive care therapy for pulmonary complications after allogeneic bone marrow transplantation (aBMT) we analysed the clinical course of ten patients requiring intubation and mechanical ventilation after aBMT for pulmonary complications. Ten out of eighty-five patients (12%) undergoing aBMT between 1989 and 1995 required mechanical ventilation for pulmonary complications at our university adult intensive care unit (ICU). Ventilation could be discontinued in four patients after pulmonary function improved. Three of these patients are long-term survivors after two to five years (median 37 months) of follow-up. Significant differences between the two groups of survivors (n = 4 patients) and non-survivors (n = 6 patients) which could have an impact on prognosis exist for graft-versus-host-disease (GvHD), (p < 0.04) and the time between aBMT and intubation (p < 0.05). There were no differences for age (median: 36 and 34 years of age respectively), laboratory values, duration of mechanical ventilation (median: 7 days for both groups) and APACHE-scores. In survivors, mechanical ventilation became necessary because of atelectasis or obstruction by mucositis in two cases, septicemia with concomitant ARDS in one case and bacterial pneumonia in one case. In non-survivors, pulmonary complications were caused by infections. Causes of death were septicemia or septic shock in five cases and GvHD-induced bronchiolitis obliterans in one case. In conclusion patients at risk for fatal outcome after intensive-care therapy for pulmonary complications following aBMT show a higher degree of GvHD, more infectious complications and a later onset of ventilation after aBMT. With an overall longterm-survival of 3 out of 10 patients, mechanical ventilation seems to be live-saving in a selected subset of patients.