Allogeneic hematopoietic stem cell transplantation for advanced mycosis fungoides and Sézary syndrome. An updated experience of the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment option in advanced-stage mycosis fungoides (MF) and Sézary syndrome (SS). This study presents an updated analysis of the initial experience of the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation (EBMT) describing the outcomes after allo-HSCT for MF and SS, with special emphasis on the impact of the use of unrelated donors (URD). METHODS AND PATIENTS: Eligible for this study were patients with advanced-stage MF or SS who underwent a first allo-HSCT from matched HLA-identical related or URD between January/1997 and December/2011. Sixty patients have been previously reported. RESULTS: 113 patients were included [77 MF (68%)]; 61 (54%) were in complete or partial remission, 86 (76%) received reduced-intensity protocols and 44 (39%) an URD allo-HSCT. With a median follow up for surviving patients of 73 months, allo-HSCT resulted in an estimated overall survival (OS) of 38% at 5 years, and a progression-free survival (PFS) of 26% at 5 years. Multivariate analysis demonstrated that advanced-phase disease (complete remission/partial remission >3, primary refractory or relapse/progression in patients that had received 3 or more lines of systemic treatment prior to transplant or the number of treatment lines was not known), a short interval between diagnosis and transplant (<18 months) were independent adverse prognostic factors for PFS; advanced-phase disease and the use of URDs were independent adverse prognostic factors for OS. CONCLUSIONS: This extended series supports that allo-HSCT is able to effectively rescue over one third of the population of patients with advanced-stage MF/SS. High relapse rate is still the major cause of failure and needs to be improved with better strategies before and after transplant. The negative impact of URD is a matter of concern and needs to be further elucidated in future studies.

Anti-herpesvirus prophylaxis, pre-emptive treatment or no treatment in adults undergoing allogeneic transplant for haematological disease: systematic review and meta-analysis.

BACKGROUND: Herpesviridae infections incur significant morbidity and indirect effects on mortality among allogeneic haematopoietic cell transplant (allo-HCT) recipients. OBJECTIVES: To study the effects of antiviral prevention strategies among haemato-oncological individuals undergoing allo-HCT. DATA SOURCES: Cochrane Central Register of Controlled Trials, MEDLINE, Embase and LILACS. We further searched for conference proceedings and trial registries. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials (RCTs). PARTICIPANTS: Adults with haematological malignancy undergoing allo-HCT. INTERVENTIONS: Antiviral prophylaxis versus no treatment/placebo or pre-emptive treatment and pre-emptive treatment versus prophylaxis with the same agent. METHODS: Random-effects meta-analysis was conducted computing pooled risk ratios (RR) with 95% CI and the inconsistency measure (I2). The certainty of the evidence was appraised by GRADE. RESULTS: We included 22 RCTs. Antiviral prophylaxis reduced all-cause mortality (RR 0.83, 95% CI 0.7-0.99; 15 trials, I2 = 0%), cytomegalovirus (CMV) disease (RR 0.54, 95% CI 0.34-0.85; n = 15, I2 = 20%) and herpes simplex virus (HSV) disease (RR 0.29, 95% CI 0.2-0.43; n = 13, I2 = 18%) compared with no treatment/placebo or pre-emptive treatment, all with high-certainty evidence. Furthermore, antivirals reduced HSV infection, CMV pneumonitis, CMV infection and varicella zoster virus disease. Anti-CMV prophylaxis (+/- pre-emptive treatment) compared with pre-emptive treatment alone reduced non-significantly all-cause mortality (RR 0.78, 95% CI 0.6-1.02; n = 8, I2 = 0%), CMV disease (RR 0.47, 95% CI 0.23-0.97; n = 9, I2 = 30%) and HSV disease (RR 0.41, 95% CI 0.24-0.67; n = 4, I2 = 0%) with high-certainty evidence, as well as CMV and HSV infections. Antiviral prophylaxis did not result in increased adverse event rates overall or more discontinuation due to adverse events. CONCLUSIONS: Antiviral prophylaxis directed against herpesviruses is highly effective and safe, reducing mortality, HSV and CMV disease, as well as herpesvirus reactivations among allo-HCT recipients. Anti-CMV prophylaxis is more effective than pre-emptive treatment alone with respect to HSV and CMV disease and infection.

Impact of conditioning with TBI in adult patients with T-cell ALL who receive a myeloablative allogeneic stem cell transplantation: a report from the acute leukemia working party of EBMT.

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a therapeutic option for adult patients with T-cell ALL (T-ALL). Meanwhile, few allo-SCT data specific to adult T-ALL have been described thus far. Specifically, the optimal myeloablative conditioning regimen is unknown. In this retrospective study, 601 patients were included. Patients received allo-SCT in CR1, CR2, CR >2 or in advanced disease in 69%, 15%, 2% and 14% of cases, respectively. With an overall follow-up of 58 months, 523 patients received a TBI-based regimen, whereas 78 patients received a chemotherapy-based regimen including IV busulfan-cyclophosphamide (IV Bu-Cy) (n=46). Unlike patients aged ⩾35 years, patients aged <35 years who received a TBI-based regimen displayed an improved outcome compared with patients who received a chemotherapy-based regimen (5-year leukemia-free survival (LFS) of 50% for TBI versus 18% for chemo-only regimen or IV Bu-Cy regimens, P=10(-5) and 10(-4), respectively). In multivariate analysis, use of TBI was associated with an improved LFS (hazard ratio (HR)=0.55 (0.34-0.86), P=0.01) and overall survival (HR=0.54 (0.34-0.87), P=0.01) in patients aged <35 years. In conclusion, younger adult patients with T-ALL entitled to receive a myeloablative allo-SCT may benefit from TBI-based regimens.

JC polyomavirus reactivation is common following allogeneic stem cell transplantation and its preemptive detection may prevent lethal complications.

Extended application of allogeneic stem cell transplantation (alloSCT) is expected to increase the frequency of JC polyomavirus (JCPyV)-related progressive multifocal leukoencephalopathy (PML). The aim of this study was to assess frequency, risk factors and course of JCPyV reactivation in allografted hematology patients. This retrospective study included consecutive adult patients, treated with alloSCT between January 2008 and December 2011. Quantitative JCPyV-PCR analysis was performed on whole blood DNA samples, originally drawn for cytomegalovirus detection since transplant date. The study included 164 patients diagnosed with hematological malignancies. Patients received reduced-intensity conditioning (n=74) or myeloablative conditioning (n=90), followed by alloSCT. Twenty patients developed transient and 20 had persistent JCPyV reactivation. Two of the patients with persistent reactivation showed a gradual increase in JCPyV levels, preceding PML development by 96 and 127 days. Cessation of immunosuppression resulted in complete resolution of neurological symptoms in one patient, while the other died of PML. Seventy percent of the 'persistently reactivating' patients died. Multivariate analysis confirmed age to be the only significant predictive factor for JCPyV reactivation. In conclusion, JCPyV reactivation occurs in a quarter of allografted patients. Preemptive detection of JCPyV reactivation in high-risk subjects and early discontinuation of immunosuppressive therapy may prevent development of lethal PML.

SCT in patients with carbapenem resistant Klebsiella pneumoniae: a single center experience with oral gentamicin for the eradication of carrier state.

Following an outbreak of carbapenem resistant Klebsiella pneumoniae (CRKP) bacteremia among inpatients in the Hemato-oncology and BMT unit, we studied the course of this infection in patients undergoing intensive chemotherapy and SCT. In addition, we conducted a pilot study aimed to eradicate CRKP colonization in the gastrointestinal tract, using oral gentamicin. Adult patients admitted to the BMT unit, identified as CRKP carriers on surveillance rectal cultures, were included in the study. Oral gentamicin at a dose of 80 mg q.i.d. was administered to all identified carriers until eradication. Among 15 colonized patients included in the study, the eradication rate achieved was 66% (10/15); discontinuation of persistent bacteremia occurred in 62.5% (5/8) and nosocomial spread of CRKP carrier state ceased. Administration of intensive chemotherapy and SCT is feasible, although associated with increased risk. Hematological patients in need of intensive chemotherapy/SCT should not be denied the required treatment on the basis of being CRKP carriers. Oral gentamicin treatment for eradication of CRKP from the gastrointestinal reservoir could serve as additional tool in the combat against the nosocomial spread and severe infections caused by this difficult-to-treat organism.

Radiological findings of early invasive pulmonary aspergillosis in immune-compromised patients.

Data on the radiological features of invasive pulmonary aspergillosis (IPA) in early stages is scanty. Detection of Aspergillus (ASP) species in broncho-alveolar (BAL) fluid by polymerase chain reaction (PCR) enables early diagnosis of IPA. This study describes the radiological features of early stages of IPA. Chest computerized tomography (CT) films of 22 consecutive immune-compromised patients with IPA diagnosed with the aid of ASP PCR testing from BAL fluid were characterized and compared to that of 18 similar patients diagnosed with traditional bacteriological methods and to data from the literature. It was found that patients diagnosed with the aid of ASP PCR testing tended to have focal disease as manifested by more 11-30 mm nodules with halo (68% vs. 33%, p = 0.04), more focal ground glass (single area 32% vs. 6%, p = 0.05, patchy 32% vs. 0%, p = 0.01) and less diffuse ground glass (0% vs. 22%, p = 0.03), less cavitations (5% vs. 28%, p = 0.05) and less consolidations (segmental 14% vs. 50%, p = 0.02 and diffuse 14% vs. 67%, p = 0.001). It was concluded that the radiological appearance of early IPA diagnosed with the aid of PCR testing included mainly discrete small nodules with halo and focal ground glass, representing the early stage of the disease.

Oral integrity and salivary profile in myeloma patients undergoing high-dose therapy followed by autologous SCT.

The underlying mechanism of high-dose therapy (HDT)-related oral mucositis (OM) may be partly mediated by alterations in the normal salivary composition. This study evaluated salivary antioxidant and immunological capacities observed in myeloma patients suffering from HDT-related OM, and assessed potential contribution of these factors to OM development. Twenty-five consecutive myeloma patients treated with melphalan 200 mg/m(2) followed by autologous SCT were enrolled. Patients underwent a daily assessment for OM, and salivary samples were collected on days -3 and +7 of transplantation and analyzed for secretory IgA and antioxidant capacity. The degree of mucosal damage was assessed by measuring the salivary carbonyl and albumin (Alb) levels. OM, reported in 96% of patients, appeared to be most severe on 8 day after transplantation (range: +2 to +14). Clinical mucositis was associated with significant reduction in salivary secretory IgA (54%; P=0.05), and antioxidant activity, measured by total antioxidant status (40%; P=0.0004), antioxidant capacity (ImAnOx) (23%; P=0.002) and uric acid level (51%; P=0.006). The increase found in salivary Alb (119%; P=0.024) and carbonyl (28%; P=0.047) levels, indicates mucosal and oxidative damage, respectively. These salivary changes might enhance mucositis development and symptoms. Therapeutic interventions, enhancing antioxidative and immunological activities need to be investigated.

Granulocyte transfusions for neutropenic patients with life-threatening infections: a single centre experience in 47 patients, who received 348 granulocyte transfusions.

INTRODUCTION: The role of granulocyte transfusions (GT) in patients with neutropenia-related infections remains controversial. MATERIALS AND METHODS: A retrospective analysis of 47 neutropenic patients, treated with 348 consecutive GTs for life-threatening infections between 1999 and 2004, is presented. RESULTS: The only grade III-IV toxicity observed in GT recipients was respiratory deterioration (n = 6, 12.8%). The overall infection-related mortality (IRM) approached 38%. Achievement of a neutrophil count of > 700 cells per microl after at least 50% of days of GTs (n = 33, 70%) significantly correlated with reduced IRM (27.3% vs. 64.3%, P < 0.02). GT doses of > 2 x 10(10) neutrophils per bag appeared to increase both neutophil and platelet counts following transfusion. CONCLUSION: GTs are safe and should be considered for patients with life-threatening neutropenic infections. However, prospective randomized studies of GTs are the only way to establish the true role of GTs.

A prospective randomized trial of itraconazole vs fluconazole for the prevention of fungal infections in patients with acute leukemia and hematopoietic stem cell transplant recipients.

Fluconazole antifungal prophylaxis is standard care in allogeneic hematopoietic stem cell transplant (HSCT) recipients, but this drug lacks anti-Aspergillus activity, the primary cause of invasive fungal infection (IFI) in many transplantation centers. We performed a randomized trial to compare itraconazole vs fluconazole, for prevention of IFIs in patients with acute leukemia (AL) and HSCT recipients. One hundred and ninety-five patients were randomly assigned to either fluconazole or itraconazole antifungal prophylaxis, after stratification into high-risk and low-risk groups. Antifungal prophylaxis was started at the beginning of chemotherapy and continued until resolution of neutropenia, or until amphotericin B treatment was started. IFI occurred in 11 (11%) of itraconazole, and in 12 (12%) fluconazole recipients. Invasive candidiasis (IC) developed in two (2%) itraconazole and one (1%) fluconazole recipients, while invasive aspergillosis (IA) developed in nine (9%) itraconazole and 11(11%) fluconazole recipients. There was no difference in the incidence of total IFI, IC and IA between the two study arms. However, there was a nonsignificant trend towards reduced mortality among patients who developed IA while receiving itraconazole prophylaxis (3/9=33% vs 8/11=73%, P=0.095).

Nosocomial outbreak of Legionella pneumophila serogroup 3 pneumonia in a new bone marrow transplant unit: evaluation, treatment and control.

A nosocomial outbreak of pneumonia caused by Legionella pneumophila serogroup 3 occurred in four patients following hematopoietic stem cell transplantation (HSCT) in a new bone marrow transplantation (BMT) unit during a 2 week period. The causative organism was recovered from the water supply system to the same unit just before the outbreak. Nineteen other BMT patients were hospitalized in the same unit at the same time, giving a frequency of proven infection of 4/23 = 17%. Immediately after recognition of the outbreak, use of tap water was forbidden, humidifiers were disconnected, and ciprofloxacin prophylaxis was started for all patients in the unit, until decontamination of the water was achieved. No other cases were detected. In conclusion, contamination of the hospital water supply system with legionella carries a high risk for legionella pneumonia among BMT patients. Early recognition of the outbreak, immediate restrictions of water use, antibiotic prophylaxis for all non-infected patients, and water decontamination, successfully terminated the outbreak.

Hepatitis C and B-cell lymphoma: the hemato-hepatologist linkage.

Hepatitis C virus (HCV)-lymphotropism may be responsible for the development of mixed cryoglobulinemia (MC) and other lymphoproliferative disorders associated with HCV infection. An association between HCV infection and B-cell lymphoma has been largely demonstrated in several geographical areas with prevalence ranging between 7.4 and 37%. However, the intimate pathogenetic mechanism involved in HCV-associated lymphomas remains considerably unknown. HCV may exerts its oncogenic potential via an indirect mechanism or utilizes other pathways directly. It is reasonable to assume that several different pathogenetic mechanisms operate in the wide spectrum of HCV-related lymphomas which includes the 'idiopathic', non-cryoglobulinemic, intermediate to high-grade lymphoma, and the more common indolent, low-grade lymphoma, preceded by long standing symptomatic MC type II. In most cases, HCV has no significant impact on response to chemotherapy or survival of lymphoma patients. Treatment with chemotherapy is relatively safe, and interruption of treatment regimens is usually not required. Whether to treat low-grade HCV-related lymphomas with anti-viral therapy is still debatable, but encouraging data emerge from recent studies.

The effect of antiviral therapy on t(14;18) translocation and immunoglobulin gene rearrangement in patients with chronic hepatitis C virus infection.

The mechanism of lymphomagenesis of hepatitis C virus (HCV)-related B-cell lymphoma is unknown. Recently, it has been suggested that HCV may induce B-cell clonal proliferation and t(14;18) translocation in patients chronically infected with the virus. Thus, this study investigated the effect of antiviral treatment on immunoglobulin heavy-chain gene (IgH) rearrangement and t(14;18) translocation in HCV infected patients. Twenty-nine patients with chronic HCV infection were studied in whom IgH rearrangement and/or t(14;18) translocation were previously detected. The IgH rearrangement (FR3/JH) and t(14;18) translocation (MBR bcl2-JH) were detected in peripheral blood mononuclear cells by polymerase chain reaction. Fifteen of 29 patients (8 with IgH rearrangement, 6 with t(14;18) translocation, and 1 with both) were treated with either interferon-alpha or by combination therapy with interferon and ribavirin for 6 to 12 months. IgH rearrangement became negative in 7 of 9 treated patients compared with only 1 of 8 of nontreated patients (P <.02). The t(14;18) translocation became negative in 6 of 7 treated patients compared with 1 of 6 nontreated patients (P =.03). Disappearance of IgH rearrangement or t(14;18) translocation was strongly associated with virologic response to treatment. Two t(14;18)+ patients developed B-cell lymphoma during follow-up. Antiviral treatment appears to be effective in eliminating the clonal proliferation of B cells in patients with chronic HCV infection and may prevent the subsequent development of lymphoma. The mechanism can be related to a direct effect of interferon-alpha on the proliferating clone or to an indirect effect by eradicating the antigenic stimulus.

bcl-2 and immunoglobulin gene rearrangement in patients with hepatitis C virus infection.

An association between chronic hepatitis C virus (HCV) infection and clonal proliferation of B cells, including B cell lymphoma, has recently been demonstrated. However, the mechanism of malignant transformation is still unknown. It has been shown that B cells from patients with type II mixed cryoglobulinaemia (MC), strongly express the antiapoptotic bcl-2 oncogene product. Therefore, we investigated a possible mechanism of lymphomagenesis, the occurrence of bcl-2 and immunoglobulin gene rearrangement (IgH) in HCV-infected patients. Three groups of patients were studied: (1) 44 patients with HCV and MC (anti-HCV and HCV RNA positive); (2) 59 patients with chronic HCV infection without MC; (3) 50 patients with chronic liver disease (CLD) not related to HCV infection. The t(14;18) translocation (MBR bcl-2-JH) and IgH rearrangement (FR3/JH) were detected by polymerase chain reaction (PCR) in peripheral mononuclear cells. bcl-2 translocation was detected in 17/44 (39%), 7/59 (12%) and in none of the patients of groups 1, 2 and 3 respectively (P < 0.01). Monoclonal IgH rearrangement was detected in 15/44 (34%), 5/59 (8.5%) and 2/50 (4%) patients of groups 1, 2 and 3 respectively (P < 0.05). HCV-infected patients had a higher prevalence of monoclonal IgH rearrangement and bcl-2 translocation than patients with CLD of other aetiologies. These data suggest that HCV may play a role in the multistep mechanism of lymphomagenesis by inducing clonal proliferation of B cells and inhibition of apoptosis.

Kinetics of factor IX activity differ from that of factor IX antigen in patients with haemophilia B receiving high-purity factor IX replacement.

Pharmacokinetic studies in haemophilia B have found in vivo recovery of FIX (FIX) to be uniformly lower than the factor VIII recovery in haemophilia A. We hypothesized that this lower recovery could result from rapid binding to high-affinity receptors on platelets and endothelium. To test this hypothesis, we evaluated the kinetics of FIX activity and protein in haemophilia B patients. Twelve patients were enrolled in a double dosing, crossover study with two high-purity FIX concentrates, AlphaNine SD and MonoNine. Subjects were given 40 U kg-1 of FIX concentrate and blood samples were taken at 15, 30, and 60 min. A second infusion of 40 U kg-1 was given after the 60 min blood sample and further blood samples removed at 15, 60, 120, and 360 min after the second dose. Patients were infused with the alternate concentrate at least 7 days later. Plasma samples were assayed for FIX activity by coagulation assay and antigen by RIA. FIX antigen in the infused concentrates was measured and quantified as microg U-1. There was no difference between the two FIX concentrates (AlphaNine vs. MonoNine) in the initial (15 min) activity (57% +/-1 19% vs. 53% +/-1 12%) and antigen (62% +/-1 16% vs. 55% +/-1 19%) recoveries. Recoveries after the second FIX dose were not statistically different than those observed after the first FIX dose. In one patient, a doubling of the initial infusion dose did not increase FIX recovery after the second FIX dose. However, the recovery of FIX antigen was significantly greater than the recovery of FIX activity and the differences became more significant in the post-15 min samples. We calculated a ratio of plasma FIX antigen to FIX activity in microg U-1. Average antigen to activity ratio increased from 5.8 +/-1 1.9 microg U-1 at 15 min to 7.1 +/-1 2.2 microg U-1 at 60 min. At 420 min the ratio increased to 9.3 +/-1 2.4 microg U-1. Although these studies failed to demonstrate a significant FIX receptor pool, they did demonstrate a phenomenon of progressive loss of biologic activity of the FIX protein after infusion of FIX concentrates.

Cancer antigen 125: a sensitive marker of ascites in patients with liver cirrhosis.

OBJECTIVE: Cancer antigen 125 (CA 125) is a high molecular mass glycoprotein, usually used for monitoring the course of epithelial ovarian cancer. Recently it has been shown that liver cirrhosis is associated with increased levels of CA 125, particularly in the presence of ascites. The aim of this study was to evaluate CA 125 as a marker for the detection of ascites in patients with chronic liver disease. METHODS: A total of 170 patients were studied. All had ultrasound scanning for detection of ascites. Group I consisted of 123 patients with chronic liver disease without ascites; whereas group II consisted of 47 patients with chronic liver disease with ascites. CA 125 levels were measured in all patients and also simultaneously in the ascitic fluid of 31 patients from group II. RESULTS: Of 47 patients, 46 (97.8%) of group II had elevated serum levels of CA 125 (mean 321 +/- 283 U/ml) as compared with only nine of 123 (7.3%) patients of group I [mean 13 +/- 15 U/ml]), p < 0.001. The mean CA 125 concentration in the ascitic fluid of 31 cirrhotic patients (group II) was 624 +/- 397 U/ml and was always higher than corresponding serum levels (p < 0.01). Serum CA 125 levels correlated with the amount of ascitic fluid (r = 0.78). A profound decrease in serum CA 125 concentration was noted 2-3 and 10 days after large volume paracentesis. CA 125 was more sensitive and preceded ultrasonography in detection of ascites in few cirrhotic patients. CONCLUSIONS: CA 125 is a highly sensitive marker to detect ascites in patients with liver cirrhosis. This marker may be useful to detect small to moderate amounts of ascitic fluid in cirrhotic patients when physical examination is difficult or equivocal for ascites.

Lack of association between hepatitis C infection and development of AIDS-related lymphoma.

Hepatitis C virus (HCV) has been associated with various lymphoproliferative disorders, and a high prevalence (9%-32%) of chronic HCV infection has been demonstrated among patients with lymphoma. Dual coinfection by HIV and HCV has been demonstrated in approximately 40% of certain populations of HIV-infected individuals. Because of this high prevalence of coinfection by HIV and HCV, the known relations between HCV and lymphoproliferative disorders, and the association of HIV and B cell lymphoma, the potential association between chronic HCV and the development of AIDS-related lymphoma was examined. The prevalence of HCV infection in HIV-infected patients with lymphoma was compared with that in patients with AIDS, diagnosed on the basis of an illness other than lymphoma. Risk factors for HCV infection, overall, were also evaluated. Evidence of HCV infection was ascertained by assessing anti-HCV antibodies, and HCV RNA in serum. The study consisted of 99 homosexual/bisexual men with AIDS-related lymphoma, and 43 other AIDS patients. HCV infection was detected in 11 of 99 (11.1 %) men with lymphoma, and in 5 of 43 (11.6%) other AIDS patients. Further, in patients with AIDS-related lymphoma, no relation was found between HCV infection and lymphoma histology or site. History of use of injected illicit drugs was associated with a significantly elevated risk of HCV infection in the combined group of lymphoma and other AIDS patients. The current study demonstrates no relation between dual infection by HIV and HCV and subsequent increased risk of lymphoma.

Liver dysfunction in patients infected with hepatitis C virus undergoing chemotherapy for hematologic malignancies.

BACKGROUND: Reactivation of chronic hepatitis B virus (HBV) infection with the development of fulminant hepatitis induced by withdrawal of chemotherapy and/or corticosteroids (CS) is well known. However, less is known about liver dysfunction in patients with hepatitis C virus (HCV) who are undergoing chemotherapy. Thus, the authors conducted this study to determine whether chemotherapy for HCV positive patients with hematologic malignancies is associated with hepatic injury. METHODS: Thirty-three consecutive HCV positive patients were studied. Twenty-six had B-cell lymphoma, two had Hodgkin's disease, two had acute myeloblastic leukemia (AML), two had chronic myelocytic leukemia, and one had multiple myeloma. HCV infection was detected by anti-HCV antibodies (enzyme immunoassay) and HCV RNA (reverse transcription polymerase chain reaction). In 28 of 33 patients, CS were used as part of the chemotherapy regimens. Liver function tests (LFTs) were evaluated prior to chemotherapy, a mean of 19 days after each cycle of chemotherapy, and during the follow-up period after the completion of chemotherapy. Mean follow-up was 14 months (range, 7-26 months). RESULTS: Twenty-seven of 33 patients (82%) were positive for both anti-HCV and HCV RNA, 5 for HCV RNA only, and 1 for anti-HCV antibodies only. Fourteen patients (42%) had normal pretreatment LFTs. During treatment, 18 patients (55%) (7 with normal and 11 with abnormal pretreatment transaminase levels) had mild-to-moderate increases of alanine aminotransferase (ALT) (median, 156 U/L; range, 59-491) and aspartate aminotransferase (AST) (median, 121; range, 45-243), which occurred 2-3 weeks after the withdrawal of chemotherapy without associated hyperbilirubinemia. Only one patient with baseline ALT and AST of 182 IU/L and 117 IU/L had a severe "flare" of hepatitis C, with peak ALT and AST of 491 IU/L and 243 IU/L. No patient developed fulminant hepatitis or died of liver-related causes. Posttreatment levels of transaminases were not significantly different from pretreatment levels. Abnormal pretreatment transaminase levels did not predict further increase during treatment. CONCLUSIONS: Significant hepatic dysfunction is uncommon among HCV infected patients treated with chemotherapy for hematologic malignancies.