Decision analysis of allogeneic hematopoietic stem cell transplantation for patients with myelodysplastic syndrome stratified according to the revised International Prognostic Scoring System.

Allogeneic hematopoietic stem cell transplantation (allo-SCT) represents the only curative treatment for patients with myelodysplastic syndrome (MDS), but involves non-negligible morbidity and mortality. Crucial questions in clinical decision-making include the definition of optimal timing of the procedure and the benefit of cytoreduction before transplant in high-risk patients. We carried out a decision analysis on 1728 MDS who received supportive care, transplantation or hypomethylating agents (HMAs). Risk assessment was based on the revised International Prognostic Scoring System (IPSS-R). We used a continuous-time multistate Markov model to describe the natural history of disease and evaluate the effect of different treatment policies on survival. Life expectancy increased when transplantation was delayed from the initial stages to intermediate IPSS-R risk (gain-of-life expectancy 5.3, 4.7 and 2.8 years for patients aged ⩽55, 60 and 65 years, respectively), and then decreased for higher risks. Modeling decision analysis on IPSS-R versus original IPSS changed transplantation policy in 29% of patients, resulting in a 2-year gain in life expectancy. In advanced stages, HMAs given before transplant is associated with a 2-year gain-of-life expectancy, especially in older patients. These results provide a preliminary evidence to maximize the effectiveness of allo-SCT in MDS.

A randomized controlled trial of rituximab for the treatment of severe cryoglobulinemic vasculitis.

OBJECTIVE: To conduct a long-term, prospective, randomized controlled trial evaluating rituximab (RTX) therapy for severe mixed cryoglobulinemia or cryoglobulinemic vasculitis (CV). METHODS: Fifty-nine patients with CV and related skin ulcers, active glomerulonephritis, or refractory peripheral neuropathy were enrolled. In CV patients who also had hepatitis C virus (HCV) infection, treatment of the HCV infection with antiviral agents had previously failed or was not indicated. Patients were randomized to the non-RTX group (to receive conventional treatment, consisting of 1 of the following 3: glucocorticoids; azathioprine or cyclophosphamide; or plasmapheresis) or the RTX group (to receive 2 infusions of 1 gm each, with a lowering of the glucocorticoid dosage when possible, and with a second course of RTX at relapse). Patients in the non-RTX group who did not respond to treatment could be switched to the RTX group. Study duration was 24 months. RESULTS: Survival of treatment at 12 months (i.e., the proportion of patients who continued taking their initial therapy), the primary end point, was statistically higher in the RTX group (64.3% versus 3.5% [P < 0.0001]), as well as at 3 months (92.9% versus 13.8% [P < 0.0001]), 6 months (71.4% versus 3.5% [P < 0.0001]), and 24 months (60.7% versus 3.5% [P < 0.0001]). The Birmingham Vasculitis Activity Score decreased only after treatment with RTX (from a mean ± SD of 11.9 ± 5.4 at baseline to 7.1 ± 5.7 at month 2; P < 0.001) up to month 24 (4.4 ± 4.6; P < 0.0001). RTX appeared to be superior therapy for all 3 target organ manifestations, and it was as effective as conventional therapy. The median duration of response to RTX was 18 months. Overall, RTX treatment was well tolerated. CONCLUSION: RTX monotherapy represents a very good option for severe CV and can be maintained over the long term in most patients.

Preliminary classification criteria for the cryoglobulinaemic vasculitis.

BACKGROUND: To develop preliminary classification criteria for the cryoglobulinaemic syndrome or cryoglobulinaemic vasculitis (CV). METHODS: Study part I developed a questionnaire for CV to be included in the formal, second part (study part II). Positivity of serum cryoglobulins was defined by experts as an essential condition for CV classification. In study part II, a core set of classification items (questionnaire, clinical and laboratory items, as agreed) was tested in three groups of patients and controls-that is, group A (new patients with the CV), group B (controls with serum cryoglobulins but lacking CV) and group C (controls without serum cryoglobulins but with features which can be observed in CV). RESULTS: In study part I (188 cases, 284 controls), a positive response to at least two of three selected questions showed a sensitivity of 81.9% and a specificity of 83.5% for CV. This questionnaire was employed and validated in study part II, which included 272 patients in group A and 228 controls in group B. The final classification criteria for CV, by pooling data from group A and group B, required the positivity of questionnaire plus clinical, questionnaire plus laboratory, or clinical plus laboratory items, or all the three, providing a sensitivity of 88.5% and a specificity of 93.6% for CV. By comparing data in group A versus group C (425 controls), the same classification criteria showed a sensitivity 88.5% and a specificity 97.0% for CV. CONCLUSION: Classification criteria for CV were developed, and now need validation.

Epidemiology and outcome of hepatocellular carcinoma in Lombardy.

BACKGROUND AND AIMS: Information on the impact of therapeutic strategies of hepatocellular carcinoma is still incomplete due to the lack of surveys involving primary-care centres. PATIENTS AND METHODS: The Gruppo Epatologico Lombardo (GEL) carried out a study on 361 incident hepatocellular carcinoma observed from January to December 1998 in 22 hospitals in Lombardy. The clinical, pathological and therapeutic data were collected from all patients; 5-year survival and factors related to outcome were analysed. RESULTS: Two hundred and ninety-seven patients were male (M/F: 4.6/1, mean age 66); 61% were HCV-pos, 15% HBV-pos, 17% alcoholic. Cirrhosis was present in 333 (92%) and was classified as Child-A in 197 (59%), Child-B in 85 (26%) and Child-C in 51 (15%) cases. Hepatocellular carcinoma was multifocal/diffuse (more than three nodules) in 91 (25%), less than three nodules in 86 (24%) and monofocal in 184 (51%) (

Successful treatment with T-depleted autologous peripheral blood stem cell transplantation of refractory chronic autoimmune thrombocytopenic purpura.

Autoimmune thrombocytopenia (AITP) is a disorder due to specific platelet auto-antibodies directed against platelet surface glycoproteins. AITP in adults is usually chronic, idiopathic and frequently refractory to conventional treatments. Myelo- and immuno-suppressive chemotherapy followed by autologous peripheral blood stem cell (PBSC) transplantation is an experimental approach for severe chronic refractory AITP. We report a case of a woman with AITP, refractory to the conventional therapy, submitted to T-cell-depleted autologous PBSC transplantation, which obtained long term stable response on platelet count. We deem that the positive outcome of our patient depends on T-cells depletion of the graft, which reduces autoreactive T clones.

Interferon-induced depression: prevalence and management.

BACKGROUND: Interferon-induced depression ranges from 0 to 50%. Interferon schedule and a history of psychiatric illnesses are not enough to predict who will develop symptoms and who will not. AIMS: To assess the prevalence of depression during interferon therapy; to test whether Minnesota Multiphasic Personality Inventory is useful in clinical practice for the early identification of patients at risk of depression; whether and how the depression can be cured. PATIENTS: One hundred and eighty-five patients treated with interferon and ribavirin for chronic hepatitis C. METHODS: Before therapy, all patients underwent a Minnesota Multiphasic Personality Inventory and a clinical examination, specifically for the identification of depressive symptoms. RESULTS: Thirty-one patients developed a psychiatric disorder, 11 of them requiring treatment with anti-depressant drugs. Among the 18 patients with Minnesota Multiphasic Personality Inventory positive tests, 16 developed a psychiatric disorder, 8 of them a severe disorder (sensitivity of 0.58; 0.73 for severe disorders). Among the 154 who did not develop psychiatric side effects, 152 had a negative Minnesota Multiphasic Personality Inventory (specificity: 0.99). Severe psychiatric disorders were successfully treated with anti-depressant drugs. CONCLUSIONS: Psychiatric side effects are easy to see during interferon therapy. A psychiatric evaluation should be considered on all patients before treatment. If depression develops, it should be treated aggressively, and selective serotonin re-uptake inhibitors are the anti-depressants of choice.

Low efficiency of a newly introduced high-density microparticles method for B cell depletion in multiple myeloma patients undergoing autologous hematopoietic stem cell transplantation.

Autologous peripheral blood stem cell (PBSC) transplantation proved to increase complete remission (CR) and DFS in multiple myeloma (MM) patients. CD34(+) cell selection has been used to reduce possible myeloma cell contamination in the graft, but it has not been showed to offer substantial advantages when compared to unpurged grafts; on the contrary, an increase of infectious complications was observed. We investigated the feasibility of a new negative-selection method in this setting. B cell negative selection was performed by using Eligix B cell HDM method. B cell contamination in the yield and in the final product was investigated by flow cytometry. Three patients with newly diagnosed MM entered the study. CD34(+) cell recovery in the three procedures was 73, 97, and 106%, and CD3(+) cell recovery was 88, 86, and 102%, respectively. CD20(+) cell depletion was 100% in all procedures, while CD19(+) cell depletion was 0.37, 1.21, and 0.07 log, respectively. We found an unexpected unreliability and a low efficiency in this B cell depletion method and suggest the need for further extensive testing before its introduction in the preclinical and clinical settings, at least in MM patients. In fact, reasons of such unsatisfactory results are still controversial: platelet contamination/activation in the preselection product, plasma protein interference, reduced CD19 antigen expression on immature B cells, lack of specificity of anti-CD19 monoclonal antibodies, instable binding between anti-CD19-coated high-density microparticles (HDM) and CD19 antigen may, alone or in combination, be involved in the system's low performance.

Red blood cell support and alloimmunization rate against erythrocyte antigens in patients undergoing hematopoietic stem cell transplantation.

We retrospectively analyzed red blood cell (RBC) support and alloimmunization rate in 218 consecutive patients - 128 from the Pediatric Department and 90 from the adult Hematology Department - undergoing hematopoietic stem cell transplantation (HSCT) between 1994 and 2000. In the pre-HSCT period, the pediatric patients undergoing auto-HSCT required more RBC support. In the post-HSCT period, pediatric patients transplanted with an unrelated donor required more RBC support (median 13.5 U/10 kg bw) than patients receiving HSCT from a related donor (median 6 U/10 kg bw) or from an autologous source (median 4 U/10 kg bw, P=0.0004). In the pre-HSCT period, 159 out of 218 patients (73%) received a total of 1843 RBC units, with an overall median of 9 U/patient over a median of 24 months (range 4-62); 10 patients (6%) developed a total of 12 alloantibodies, with an alloimmunization rate of 5.4/1000 RBC units. In the post-HSCT period, all but three patients were given a total of 2420 RBC units, with an overall median of 6 U/patient over a median of 4 months (range 1-18); all but one of the pre-existing alloantibodies disappeared and three patients (1%) developed new alloantibodies with an alloimmunization rate of 1.2/1000 RBC units. These newly produced alloantibodies (one anti-M and two anti-E) were detected at +58, +90 and +210 days after HSCT. These findings might suggest a different approach to alloantibody screening tests in patients receiving HSCT, with a subsequent reduction of costs and laboratory workload.

Outcome of liver disease in a large cohort of histologically proven chronic hepatitis C: influence of HCV genotype.

OBJECTIVE: To assess the influence of hepatitis C virus (HCV) genotypes on the clinical outcome of liver disease, we analysed 2,307 patients. RESULTS: The most frequently represented genotypes were 1b (40%) and 2 (28.1%). Patients with these genotypes had a median age higher than patients with other genotypes (P< 0.01). The overall survival of subjects with genotype 1b was poorer than the survival of patients with other genotypes (P< 0.01). Liver cirrhosis was found in 280 patients (12.1%), and type 1b was the most represented isolate among them (P< 0.01). Sixty-two patients (22%) developed hepatocellular carcinoma (HCC) during a follow-up of 1481.8 cumulative years (estimated crude incidence rate, 4.1 cases per 100 person-years for all cirrhotics; 5.9 cases for genotype 1a; 4.5 cases for genotype 1b; and 2.8 cases for genotypes non-1). Considering the whole population of 2,307 patients, only genotype 1b was associated significantly with both cirrhosis and the development of HCC. One hundred and nineteen cirrhotic patients underwent treatment with interferon in uncontrolled studies. Interferon therapy was associated with both better survival (P< 0.01) and a lower cumulative hazard for HCC (P< 0.01). CONCLUSIONS: Genotype 1b was associated with a poorer prognosis, probably because it leads to cirrhosis and consequently to HCC development. However, our data did not confirm genotype 1b as an independent risk factor for HCC in liver cirrhosis, which plays a major role in carcinogenesis. Interferon should be considered as a useful strategy in cirrhosis for improvement of survival and reduction of HCC risk.

Sensitivity to the abl inhibitor STI571 in fresh leukaemic cells obtained from chronic myelogenous leukaemia patients in different stages of disease.

STI571 (CGP57148B) is an inhibitor of BCR/ABL, the cause of chronic myeloid leukaemia (CML). A difference exists between CML patients in chronic phase, in which responses to STI571are durable, and patients in blast crisis, who generally experience only transient responses. Leukaemic cells from six CML patients from whom samples could be obtained during chronic phase and at the time of blast crisis (BC) were compared for sensitivity to STI571, using an in vitro assay. BC samples showed a sensitivity similar to that obtained during chronic phase, suggesting that no substantial intrinsic resistance to STI571 was present in BC.

Incidence and outcome of pneumonia in patients with acute leukemia receiving first induction therapy with anthracycline-containing regimens.

BACKGROUND AND OBJECTIVES: Even though the risk of pneumonia is higher in patients with advanced disease, the potential risk of death is particularly relevant during induction therapy, when patients can be potentially cured of their hematologic disease: our study was aimed at evaluating the risk and outcome of pneumonia in these patients. DESIGN AND METHODS: We retrospectively studied all 458 patients affected by acute leukemia receiving an anthracycline-containing induction regimen in the years 1984-1989. RESULTS: Of the 458 patients, 109 (23.8%) developed pneumonia: 91 had acute myelogenous leukemia (AML) and 18 had acute lymphoblastic leukemia (ALL). At univariate analysis, advanced age, AML and total blast count significantly correlated with the risk of pneumonia. At multivariate analysis, only age (p< 0.0001) and total blast count (p=0.002) retained their prognostic significance. Pneumonia responded to treatment in 67 (61.5%) patients, while 42 (38.5%) patients died. Among patients with pneumonia, 51 (46.8%) patients achieved a complete remission: 9/18 ALL and 42/91 AML. At univariate analysis, the most significant determinant of a positive outcome was the achievement of complete remission; a higher absolute neutrophil count at the onset of pneumonia, the absence of rales, a single infiltrate and the absence of microbiological demonstration of infection were also related to a positive outcome. At multivariate analysis, the achievement of complete remission and, with borderline significance, a single infiltrate maintained their prognostic value. INTERPRETATION AND CONCLUSIONS: Pneumonia remains one of the most relevant risks of morbidity and mortality during induction therapy for acute leukemia. A fatal outcome is associated, in most cases, with a failure to achieve remission of leukemia.

Role of alpha1 acid glycoprotein in the in vivo resistance of human BCR-ABL(+) leukemic cells to the abl inhibitor STI571.

BACKGROUND: Chronic myeloid leukemia is caused by a chromosomal translocation that results in an oncogenic fusion protein, Bcr-Abl. Bcr-Abl is a tyrosine kinase whose activity is inhibited by the antineoplastic drug STI571. This drug can cure mice given an injection of human leukemic cells, but treatment ultimately fails in animals that have large tumors when treatment is initiated. We created a mouse model to explore the mechanism of resistance in vivo. METHODS Nude mice were injected with KU812 Bcr-Abl(+) human leukemic cells. After 1 day (no evident tumors), 8 days, or 15 days (tumors >1 g), mice were treated with STI571 (160 mg/kg every 8 hours). Cells recovered from relapsing animals were used for in vitro experiments. Statistical tests were two-sided. RESULTS: Tumors regressed initially in all STI571-treated mice, but all mice treated 15 days after injection of tumor cells eventually relapsed. Relapsed animals did not respond to further STI571 treatment, and their Bcr-Abl kinase activity in vivo was not inhibited by STI571, despite high plasma concentrations of the drug. However, tumor cells from resistant animals were sensitive to STI571 in vitro, suggesting that a molecule in the plasma of relapsed animals may inactivate the drug. The plasma protein alpha1 acid glycoprotein (AGP) bound STI571 at physiologic concentrations in vitro and blocked the ability of STI571 to inhibit Bcr-Abl kinase activity in a dose-dependent manner. Plasma AGP concentrations were strongly associated with tumor load. Erythromycin competed with STI571 for AGP binding. When animals bearing large tumors were treated with STI571 alone or with a combination of STI571 and erythromycin, greater tumor reductions and better long-term tumor-free survival (10 of 12 versus one of 13 at day 180; P:<.001) were observed after the combination treatment. CONCLUSION: AGP in the plasma of relapsed animals binds to STI571, preventing this compound from inhibiting the Bcr/Abl tyrosine kinase. Molecules such as erythromycin that compete with STI571 for binding to AGP may enhance the therapeutic potential of this drug.

Depression during interferon therapy for chronic viral hepatitis: early identification of patients at risk by means of a computerized test.

OBJECTIVES: At the doses used for the treatment of chronic viral hepatitis, interferon (IFN)-related side-effects are usually modest, even though in some cases they require the interruption of therapy. Neuropsychiatric disturbances that range from modest depression and irritability to forms of manic-depressive psychosis and attempted or successful suicides are among the most important side-effects. The aim of our study was to determine whether the Minnesota Multiphasic Personality Inventory (MMPI) is a sensitive and reliable test for the early identification of patients at risk of depression before IFN therapy is commenced, and whether it could be useful for the monitoring of these patients during treatment. METHODS: We prospectively studied 67 patients with chronic active liver diseases, consecutively enrolled in open studies and treated with r-IFNalpha2. Before starting therapy and after 3 months of treatment, all patients underwent a clinical neurological evaluation and MMPI. RESULTS: At baseline, the correlation between the clinical evaluation and the score of the depression scale of the MMPI was statistically significant (P< 0.0001). Nine of 14 (64.3%) patients with a baseline score > or = 60/100 showed a depressive mood after 3 months of therapy. Five of 44 patients (11.3%) with a baseline score < 60/100 showed a depression of medium level after 3 months of treatment. This difference was highly significant (P< 0.0001). CONCLUSIONS: According to our results, the MMPI is a reliable and sensitive test for the early identification of patients at risk of depression before and during IFN therapy for chronic viral liver diseases.

Hepatitis C virus in non-Hodgkin's lymphoma. A reappraisal after a prospective case-control study of 300 patients. Lombart Study Group of HCV-Lymphoma.

It is widely thought, but not yet explained, that there might be a pathogenetic link between the infection of hepatitis C virus (HCV) and the onset of B non-Hodgkin's lymphoma (NHL). We studied the prevalence of serum anti-HCV antibodies among 300 NHL comparing it with the prevalence among 600 age- and sex-matched non-neoplastic subjects as controls, 247 patients with non-lymphomatous neoplasm, and 122 patients treated with immunosuppressive agents. We found a prevalence of 0.16 among NHL and 0.085 among controls and non-lymphomatous patients. Although the difference was statistically significant (P < 0.001), the odds ratio was 2.049 and its confidence intervals included the equality. The HCV prevalence was independent of NHL subset, and the genotypes distribution was the same among NHL and controls. We disclosed a HBsAg prevalence of 0.077 in NHL versus 0.008 in controls (P < 0.001) with an odds ratio of 9.9. We do not believe that these findings support the hypothesis of an HCV pathogenetic role in lymphomagenesis because (i) the risk of previous infection is marginally higher in NHL than in controls, (ii) a typical genotype distribution is lacking, as is a NHL clinico-histological feature associated with HCV, and (iii) the higher prevalence of viral infection is not specific as witnessed by the high HBsAg prevalence.

Differential recognition of a BCR/ABL peptide by lymphocytes from normal donors and chronic myeloid leukemia patients.

The BCR/ABL oncogenic fusion protein transforms normal bone marrow stem cells into neoplastic cells. It has been shown that peptides derived from the junctional region of this oncogenic fusion protein can be recognized by human T-lymphocytes obtained from normal donors. In this study, we investigated the immunogenicity in patients with chronic myeloid leukemia (CML) of a 17 mer b3/a2 Bcr/abl peptide (B/A1), which was shown to induce proliferative responses in lymphocytes from normal donors. A total of 56 CML patients in chronic phase were studied. Twenty-two patients were studied at diagnosis without any treatment (group I). Fourteen patients were receiving IFN (group II), 14 patients were being treated with hydroxyurea (group III), and 6 patients were on different regimens (group IV). Patients were initially assessed for general immunological competence using both in vivo and in vitro assays. Patients were also selected for the expression of HLA-DR0401, the HLA specificity known to present peptide B/A1 to CD4 lymphocytes. With the exception of the six patients in group IV, the results of all these assays (in vitro phytohemagglutinin/tetanus toxoid responses, in vivo skin reaction to ubiquitous antigens) in CML patients did not significantly differ from those obtained in normal donors, thus excluding the presence of generalized immunosuppression. Eight patients with HLA-DR0401 and a b3/a2 type of fusion were identified and further studied. In these eight patients dendritic cells were obtained from adherent peripheral blood mononuclear cells and used to stimulate CD4 lymphocytes. No patient developed a specific response to the bcr/abl peptide, although patients' lymphocytes proliferated in response to a promiscuous tetanus toxoid peptide in all but one case. In contrast, response to the bcr/abl peptide was observed in seven of eight HLA-DR0401 healthy donors tested. These data suggest that immunocompetent, HLA-DR0401+ CML patients are unable to respond to peptide B/A1, at difference from healthy donors. The implication of these results for the immunotherapy of CML is discussed.

Defibrotide in recurrent thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura (TTP) is a common illness characterized by platelet thrombi within the microvascularization. In its natural course, this disease has had a mortality rate of 90%. Plasma infusion or exchange achieved a survival rate of 70% to 90%. However, 10% to 30% of patients surviving the initial TTP episode relapse at regular intervals. The treatment of recurrent forms of the disease remains a challenge; several approaches have been shown to induce medium to long term remissions. We describe a patient with recurrent TTP whose disease remitted after administration of defibrotide.

The tyrosine kinase abl-related gene ARG is fused to ETV6 in an AML-M4Eo patient with a t(1;12)(q25;p13): molecular cloning of both reciprocal transcripts.

The Ets variant gene 6 (ETV6/TEL) gene is rearranged in the majority of patients with 12p13 translocations fused to a number of different partners. We present here a case of acute myeloid leukemia M4 with eosinophilia (AML-M4Eo) positive for the CBFb/MYH11 rearrangement and carrying a t(1;12)(q25;p13) that involves the ETV6 gene at 12p13. By 3'rapid amplification of cDNA ends-polymerase chain reaction (3'RACE-PCR), a novel fusion transcript was identified between the ETV6 and the Abelson-related gene (ARG) at 1q25, resulting in a chimeric protein consisting of the HLH oligomerization domain of ETV6 and the SH2, SH3, and protein tyrosine kinase (PTK) domains of ARG. The reciprocal transcript ARG-ETV6 was also detected in the patient RNA by reverse transcriptase-polymerase chain reaction (RT-PCR), although at a lower expression level. The ARG gene encodes for a nonreceptor tyrosine kinase characterized by high homology with c-Abl in the TK, SH2, and SH3 domains. This is the first report on ARG involvement in a human malignancy.

Electrolyte monitoring in patients undergoing peripheral blood stem cell collection.

In recent years peripheral blood stem cell (PBSC) collection for allogeneic or autologous transplantation has experienced an increased use in the onco-hematological setting. The latest generation cell separators allow a satisfactory and safe PBSC collection. Nevertheless, as in all therapeutic apheresis procedures, patients may experience procedure-related side-effects, mainly vasovagal reactions or symptoms related to hypocalcemia and/or hypomagnesemia. We investigated electrolyte changes in 18 patients, with a median age of 46 years (range 7-62), undergoing PBSC collection from January to April 1998. A significant decrease in total calcium in the final sample (9.65 +/- 0.7 mg/dL) with respect to the basal one (9.2 +/- 0.6 mg/dL, P < 0.05) was observed; also ionized calcium decreased markedly from the first sample drawn at +30 minutes: 1.22 +/- 0.14 vs. 1.03 +/- 0.15 mmol/L (P < 0.05), and a highly significant difference emerged when basal value were compared to the final value: 1.22 +/- 0.14 vs. 0.94 +/- 0.13 mmol/L (P < 0.0001). Similar findings affected potassium concentration: 4.1 +/- 0.4 vs. 3.3 +/- 0.3 mEq/L (P < 0.0001). Three out of eighteen patients (16.7%) reached a final potassium level <3.0 mEq/L, and eight out of eighteen (44.5%) showed a potassium concentration decrease >20% with respect to the basal value. A mild metabolic alkalosis occurred during the procedure: pH increased from 7.35 +/- 0.02 to 7.43 +/- 0.028 (P < 0.001), and plasma bicarbonate concentration increased from 27.48 +/- 2.21 to 32.44 +/- 2.52 mmol/L (P < 0.01). Sodium and chloride did not differ in the final sample with respect to the basal sample. None of our patients experienced clinically relevant side effects related to severe electrolyte changes (i.e., >20% with respect to the basal value). Because our current therapeutic schedules include patients older than 50 years in the PBSC collection and transplantation program and since it is well known that subclinical myocardial disease may occur in up to 4% of middle-aged males, we suggest that patients aged 50 or older undergoing PBSC collection procedures be carefully monitored in order to identify significant electrolyte variation, especially if they present with low serum potassium levels. However, further investigation of larger patient series are needed to determine the clinical relevance of serum potassium changes during apheresis.