Recent improvement in outcome of unrelated donor transplantation for aplastic anemia.

The aim was to determine whether outcome of unrelated donor transplantation for severe aplastic anemia has improved in recent years and whether this is due to patient selection or better transplant technology. We analyzed 498 patients transplanted during 1990-2005. By running univariate regression models dichotomizing year of transplantation we defined 1998 as the year of the most significant change in survival. Five-year survival increased from 32+/-8% before 1998 to 57+/-8% after 1998 (P<0.0001). When comparing the cohort before (n=149) and after 1998 (n=349), there were no differences except for older age, and more frequent use of PBSCs, after 1998. High-resolution HLA typing data were unavailable. After 1998, there was less graft failure (11 vs 26%, P<0.0001), less acute GvHD (cumulative incidence 28 vs 37%, P=0.02) and less chronic GvHD (22 vs 38%, P=0.004). In multivariate analyses adjusting for differences in age, HLA-mismatch, performance score and time to transplantation, there was no change in the year of transplant effect (relative risk of death in transplants after 1998: 0.44 (95% confidence interval 0.33-0.59)). There is no evidence for patient selection to explain significantly improved survival in patients transplanted after 1998. We speculate that this is due to better donor matching.

A novel Leu153Ser mutation of the Fanconi anemia FANCD2 gene is associated with severe chemotherapy toxicity in a pediatric T-cell acute lymphoblastic leukemia.

Fanconi anemia (FA) is an autosomal recessive disease characterized by pancitopenia, congenital malformations, predisposition to cancers and chromosomal instability. We report the clinical and molecular features of a patient initially identified as a potential FA case only because of chemotherapy toxicity during the treatment of a T-lineage acute lymphoblastic leukemia (ALL). Cells from this patient showed a moderate chromosomal instability, increasing sensitivity to DNA crosslinking agents but normal response to ionizing radiation. The analysis of FA proteins demonstrated a marked reduction of FANCD2 (>95%), but normal levels of FANCA or FANCG. Interestingly, this defect was associated with a homozygous missense mutation of FANCD2, resulting in a novel amino-acid substitution (Leu153Ser) at residue Leu153, which is highly conserved through evolution. The FANCD2(L153S) protein, whose reduced expression was not due to impaired transcription, was detected also in its monoubiquitinated form in the nucleus, suggesting that the mutation does not affect post-translation modifications or subcellular localization but rather the stability of FANCD2. Therefore, the hypomorphic Leu153Ser mutation represents the first example of a FANCD2 defect that might promote clonal progression of tumors, such as T-ALL, and severe chemotherapy toxicity in patients without any clinical manifestations typical of FA.

Allogeneic stem cell transplantation following reduced-intensity conditioning can induce durable clinical and molecular remissions in relapsed lymphomas: pre-transplant disease status and histotype heavily influence outcome.

The safety and efficacy of reduced-intensity conditioning (RIC) followed by allogeneic stem cell transplantation (SCT) for relapsed lymphomas remains unresolved. We conducted a prospective, multicentered, phase II trial. A total of 170 relapsed/refractory lymphomas received a RIC regimen followed by SCT from sibling donors. The primary study end point was non-relapse mortality (NRM). Histologies were non-Hodgkin's lymphomas (NHL) (indolent (LG-NHL), n=63; aggressive (HG-NHL), n=61; mantle cell lymphoma (MCL), n=14) and Hodgkin's disease (HD, n=32). Median follow-up was 33 months (range, 12-82). The results show that frequencies were as follows: cumulative NRM at 3 years, 14%; acute and chronic graft-versus-host disease (GVHD) 35 and 52%, respectively; 3-year overall survival (OS), 69% for LG-NHL, 69% for HG-NHL, 45% for MCL and 32% for HD (P=0.058); and 3-year relapse incidence, 29, 31, 35 and 81%, respectively (P<0.001). Relapse risk differed significantly at 3 years between follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL) (14 versus 46%, P=0.04). Molecular remission occurred in 94 and 40% (P=0.002) of patients with FL and CLL, respectively. On multivariate analysis, OS was influenced by chemorefractory disease (hazard ratio (HR)=3.6), diagnosis of HD (HR=3.5), and acute GVHD (HR=5.9). RIC allogeneic SCT is a feasible and effective salvage strategy in both indolent and aggressive NHL.

The influence of cyclosporin alone, or cyclosporin and methotrexate, on the incidence of mixed haematopoietic chimaerism following allogeneic sibling bone marrow transplantation for severe aplastic anaemia.

We previously reported a randomized trial comparing Cyclosporin-A (CsA) and short-term methotrexate versus CsA alone for graft-versus-host disease (GvHD) prophylaxis in 71 patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT) from a human leucocyte antigen-identical sibling for severe aplastic anaemia (SAA). We found a better survival in the group receiving the two-drug prophylaxis regimen with no significant difference in the probability of developing GvHD between the two groups. The present study details chimaeric analysis and its influence on survival and GvHD occurrence in 45 of the original 71 patients in whom serial samples were available. Analysis was carried out in a blinded prospective manner. Seventy-two per cent achieved complete donor chimaerism (DC), 11% stable mixed chimaerism (SMC) and 17% progressive mixed chimaerism (PMC). The overall 5-year survival probability was 82% (+/-11%) with a significant survival advantage (P = 0.0009) in DC or SMC compared to those with PMC. Chronic GvHD was more frequent in DC patients, whereas no patient with SMC developed chronic GvHD. Graft failure occurred in 50% of the PMC group. This study demonstrates the relevance of chimaerism analysis in patients receiving HSCT for SAA and confirms the occurrence of mixed chimaerism in a significant proportion of recipients.

Efficacy of caspofungin as secondary prophylaxis in patients undergoing allogeneic stem cell transplantation with prior pulmonary and/or systemic fungal infection.

Transplanted patients with a history of invasive fungal infection (IFI) are at high risk of developing relapse and fatal complications. Eighteen patients affected by hematological malignancies and a previous IFI were submitted to allogeneic stem cell transplantation, using Caspofungin as a secondary prophylaxis. Patients had a probable or proven fungal infection and 16 had a pulmonary localization. No side effects were recorded during treatment with Caspofungin. Compared to pre-transplant evaluation, stability or improvement of the previous IFI was observed in 16 of the 18 patients at day 30, in 13 of the 15 evaluable patients at day 180 and in 11 of the 11 evaluable patients at day 360 post transplant. In particular, all the six patients with a proven fungal infection were alive, with a stable or improved IFI after 1 year from transplant. At a maximum follow-up of 31 months, eight patients died for disease progression or transplant-related complications, but only two had evidence of fungal progression. Secondary prophylaxis with Caspofungin may represent a suitable approach to limit IFI relapse or progression, allowing patients with hematological malignancies to adhere to the planned therapeutic program.

Genomic gain at 6p21: a new cryptic molecular rearrangement in secondary myelodysplastic syndrome and acute myeloid leukemia.

Fluorescence in situ hybridization and comparative genomic hybridization characterized 6p rearrangements in eight primary and in 10 secondary myeloid disorders (including one patient with Fanconi anemia) and found different molecular lesions in each group. In primary disorders, 6p abnormalities, isolated in six patients, were highly heterogeneous with different breakpoints along the 6p arm. Reciprocal translocations were found in seven. In the 10 patients with secondary acute myeloid leukemia/myelodysplastic syndrome (AML/MDS), the short arm of chromosome 6 was involved in unbalanced translocations in 7. The other three patients showed full or partial trisomy of the 6p arm, that is, i(6)(p10) (one patient) and dup(6)(p) (two patients). In 5/7 patients with unbalanced translocations, DNA sequences were overrepresented at band 6p21 as either cryptic duplications (three patients) or cryptic low-copy gains (two patients). In the eight patients with cytogenetic or cryptic 6p gains, we identified a common overrepresented region extending for 5-6 megabases from the TNF gene to the ETV-7 gene. 6p abnormalities were isolated karyotype changes in four patients. Consequently, in secondary AML/MDS, we hypothesize that 6p gains are major pathogenetic events arising from acquired and/or congenital genomic instability.

Effect of age and previous autologous transplantation on nonrelapse mortality and survival in patients treated with reduced-intensity conditioning and allografting for advanced hematologic malignancies.

PURPOSE: Older age and a previously failed autologous stem-cell transplantation (SCT) are poor prognostic factors for patients receiving myeloablative conditioning and allogeneic SCT. Reduced-intensity conditioning (RIC) regimens achieved a significant reduction of treatment-related mortality, but the influence of previously described risk factors on the outcome of this novel transplantation strategy have not been fully analyzed yet. PATIENTS AND METHODS: One hundred fifty patients with advanced hematologic malignancies received a RIC regimen containing thiotepa (10 mg/kg), fludarabine (60 mg/m2), and cyclophosphamide (60 mg/kg), followed by an allogeneic transplantation from an HLA-identical sibling donor. Patients were divided into two cohorts according to age; 90 patients were younger than 55 years, and 60 patients were 55 years old or older. The other pretransplantation characteristics were fairly balanced. RESULTS: Actuarial 5-year nonrelapse mortality (NRM) rate was not statistically different between the groups (13% in the younger group and 19% in the older group). By univariate and multivariate analysis, NRM was significantly higher in older patients who previously experienced failure with an autograft. The occurrence of grade 3 to 4 acute graft-versus-host disease (GVHD) or extensive chronic GVHD was associated with a higher NRM in both age cohorts. Overall survival (OS) was not statistically different between the younger (66%) and older groups (61%). By multivariate analysis, refractory disease was associated with a worse OS irrespective of age group. CONCLUSION: RIC transplantations show a rather low NRM, and age > or = 55 years per se cannot be considered a risk factor anymore. The timing of transplantation and novel strategies for the prevention of severe GVHD could further improve patient outcome.

Comparison of long-term outcomes after allogeneic hematopoietic stem cell transplantation from matched sibling and unrelated donors.

Long-term survivors of hematopoietic stem cell transplants remain at risk of potentially fatal complications that detract from life quality. Long-term morbidity and mortality were compared between matched recipient cohorts surviving 2 or more years and defined by donor type, HLA matched sibling donor (MSD) or volunteer unrelated donor (URD). Patients were previously entered into the prospective multicenter International Unrelated Search and Transplant Study. Thirty-nine centers provided data on 108 URD and 355 MSD recipients surviving more than 2 years. Long-term survival, performance status, chronic GvHD (c-GvHD), secondary malignancy, endocrine dysfunction, cataracts, bone necrosis and dental pathology were compared between cohorts. Twelve year survival was 77+/-5% for the MSD and 67+/-11% for the URD cohort (P=0.1). Late death occurred in 105 of 463 recipients alive at 2 years, 73 after 355 (21%) MSD and 32 after 108 (30%) URD transplants, P=0.10. Of 105 deaths, the cause was relapse in 60 and unrelated to relapse in 45 cases. Cumulative incidence of extensive c-GvHD (P=0.002), cataracts (P=0.02) and bone necrosis (P=0.02) was higher after URD transplants. No long-term difference in endocrine dysfunction, secondary malignancy and major dental pathology was detected. This landmark study will assist physicians counseling patients pre-transplant and with their long-term care post transplant.

Microgranular variant of acute promyelocytic leukemia in children.

PURPOSE: The microgranular variant (M3v) of acute promyelocytic leukemia (APL) rarely has been reported in a pediatric series of acute nonlymphoblastic leukemia (AnLL). We reviewed the clinical and biologic features of childhood M3v cases in our AnLL series. PATIENTS AND METHODS: From January 1970 to January 1991, 11 children with M3v were admitted and treated at our center. A diagnosis was made according to French-American-British (FAB) criteria. Morphologic examination, cytochemical analysis, and immunophenotyping were performed by a single pathologist. From January 1984, the diagnosis was confirmed by cytogenetic and, subsequently, by molecular analysis on frozen material. RESULTS: In our series, the overall incidence of children with APL was unusually high, 31.2% of the AnLL and M3v constituted one case in every four cases of APL. Even restriction of the analysis to the time when either cytogenetic and DNA studies confirmed the diagnosis, the incidence did not change. The immunophenotype of M3v cases was identical to that described for the hypergranular type, but an unexpected association of CD2 with M3v was shown. The onset was characterized by marked hyperleukocytosis (median WBC count, 87 x 10(9)/L) unlike classic APL. Disseminated intravascular coagulation (DIC) was always present and severe. Hyperleukocytosis and DIC were responsible for the high incidence of deaths for hemorrhagic events in the first days after onset (eight of 11 patients). CONCLUSIONS: In our experience, for unknown reasons, M3v may occur in childhood more than generally was considered. The clinical course and prognosis seem worse in M3v than in typical APL cases.

Fludarabine, cyclophosphamide and anti-thymocyte globulin for alternative donor transplants in acquired severe aplastic anemia: a report from the EBMT-SAA Working Party.

We have developed a reduced-intensity conditioning regimen for patients with severe aplastic anemia (SAA) undergoing alternative donor transplants, which includes fludarabine (120 mg/m(2)), cyclophosphamide (1,200 mg/m(2)) and antithymocyte globulin (7.5 mg/kg). Graft-versus-host disease (GvHD) prophylaxis consisted of cyclosporine and methotrexate. We have enrolled 38 SAA patients in this trial: median age of 14 (3-37) years, transplanted from unrelated (n=33) or family mismatched (n=5) donors, with unmanipulated marrow (n=36) or peripheral blood (n=2). Seven patients (18%) had evidence of graft failure, 11% developed grade II-III acute GvHD and 27% developed chronic GvHD. The actuarial 2-year survival is 73%, with a median follow-up of 621 days. Younger patients (

Vaccination of stem cell transplant recipients: recommendations of the Infectious Diseases Working Party of the EBMT.

Over the last 25 years, the numbers of hematopoietic stem cell transplant (SCT) patients have increased rapidly. Infections have been major obstacles for successful transplantation. Thus, infection prevention is very important in transplant recipients. As the results of transplantation have improved, the number of long-term survivors has increased. Vaccination is a potentially important strategy for reducing the risk for vaccine-preventable infections after SCT. The EBMT produced recommendations for vaccination of SCT recipients published in Bone Marrow Transplantation in 1995. This paper updates the previous recommendations based on current knowledge.

The polymorphisms -318C>T in the promoter and 49A>G in exon 1 of CTLA4 and the risk of aplastic anemia in a Caucasian population.

Aplastic anemia (AA) is a rare disease with a major autoimmune pathogenetic component. CTLA4 is a T-lymphocyte surface molecule involved in the maintenance of immune tolerance. Some polymorphisms associated with a reduced expression of CTLA4, and thus presumably with increased tendency to autoimmunity, have been associated with various autoimmune diseases. In this study, we evaluated the distribution of the low expression polymorphisms -318C > T and 49A > G of CTLA4 in a population of 67 patients with acquired AA and in 100 normal controls. There was no difference in the distribution of the tested polymorphism between patients and controls and, within the patient group, between those who responded to immunosuppression vs those who did not respond. This study indicates that the polymorphisms -318C > T and 49A > G of CTLA4 do not affect the risk of developing AA and do not influence the response to immunosuppression.

Treatment of acquired severe aplastic anemia: bone marrow transplantation compared with immunosuppressive therapy--The European Group for Blood and Marrow Transplantation experience.

Patients with severe aplastic anemia (SAA) can be successfully treated with bone marrow transplantation (BMT) or immunosuppressive therapy (IS). The current outcome using both forms of therapy among 3,669 patients treated in Europe between 1976 and 1998 is reviewed. Significant progress has been made and the overall risk of failure is now low, with survival rates greater than 80% for both treatments. Chronic graft-versus-host disease (GvHD) remains a problem for BMT patients, and carries a high risk of lethal complications. On the other hand, IS patients are exposed to late failure due to relapse or clonal/malignant diseases. First-line BMT from identical siblings is compared with IS therapy in an intent-to-treat analysis of 1,765 patients, regardless of subsequent transplant status. The outcome of SAA patients has improved considerably over time and is influenced by patient variables such as severity of the disease and age, but also by the choice of the initial treatment.

Cataracts after total body irradiation and bone marrow transplantation in patients with acute leukemia in complete remission: a study of the European Group for Blood and Marrow Transplantation.

PURPOSE: Advances in bone marrow transplantation (BMT) have consistently improved long-term survival. Therefore, evaluation of late complications such as cataracts is of paramount importance. METHODS AND MATERIALS: We analyzed data of 2149 patients from the EBMT registry. A cohort of 1063 patients were evaluable for survival and ophthalmologic status after transplant for acute leukemia (AL) in first or second complete remission. Conditioning therapy included either single-dose total body irradiation (STBI) or fractionated TBI (FTBI) grouped in different dose rates (low: LDR < or = 0.04 Gy/min; high: HDR > 0.04 Gy/min). RESULTS: The overall 10-year estimated cataract incidence (ECI) was 50%. It was 60% in the STBI group, 43% in the FTBI group < or = 6 fractions, and 7% in the FTBI group > 6 fractions (p < 10(-4)). It was significantly lower (30%) in the LDR than in the HDR groups (59%;p < 10(-4)). Patients receiving heparin for veno-occlusive disease prophylaxis had fewer cataracts than those who did not (10-year ECI: 33% vs. 53%, respectively;p = 0.04). The 10-year ECI was 65% in the allogeneic vs. 46% in the autologous BMT patients (p = 0.0018). Factors independently associated with an increased risk of cataract were an older age (> 23 years), higher dose rate (> 0.04 Gy/min), allogeneic BMT, and steroid administration (> 100 days). The use of FTBI was associated with a decreased risk of cataract. Heparin administration was a protective factor in patients receiving STBI. In terms of cataract surgery, the unfavorable factors for requiring surgery were: age > 23 yr, STBI, dose rate > 0.04 Gy/min, chronic graft-vs.-host disease (cGvHD), and absence of heparin administration. Among the patients who required cataract surgery (111 out of 257), secondary posterior capsular opacification was observed in 15.7%. CONCLUSION: High dose rate and STBI are the main risk factors for cataract development and the need for surgery, and the administration of heparin has a protective role in cataractogenesis.

Predictability before transplant of hepatic complications following allogeneic bone marrow transplantation.

This study was undertaken to evaluate the occurrence of VOD and other liver diseases following BMT in a patient population with a high incidence of hepatitis before conditioning regimen. We prospectively reviewed 186 consecutive patients undergoing BMT from 1976 to 1986 to determine incidence and type of liver disease after BMT and predisposing factors. Two of 186 patients experienced VOD (1.07%). Acute and chronic liver GVHD were found in 25.8% and 36% of the patients, respectively. Acute hepatitis (AH) was diagnosed in 29.4% and chronic hepatitis (CH) in 42.6% of the patients. Statistical analysis showed no influence of pretransplant variables on the occurrence of acute GVHD and AH; there was a weak correlation (P = 0.01) between pre-BMT abnormal transaminases and occurrence of chronic GVHD. Contingency table and Cox analysis showed a greater risk of CH for patients with abnormal pretransplant SGPT levels (P = 0.0004 and P = 0.0022). No other variables could be associated with posttransplant CH. Actuarial survival was 71% versus 69% for patients with normal versus abnormal transaminases (P = 0.2). As VOD was a rare event, despite 53% of patients having abnormal transaminase values before transplant, we suggest that a lower and slower TBI is more important than pretransplant normal transaminases in preventing this complication. We conclude that evidence of compensated hepatitis is not a relative contraindication for BMT.

The role of hepatitis C and B virus infections as risk factors for severe liver complications following allogeneic BMT: a prospective study by the Infectious Disease Working Party of the European Blood and Marrow Transplantation Group.

BACKGROUND: Severe liver disease, including fulminant hepatic failure and venoocclusive disease can occur after bone marrow transplantation (BMT). The aim of our study was to assess risk factors for veno occlusive disease and severe liver disease occurring within 6 months from BMT. METHODS: A total of 193 consecutive patients from 15 BMT Centers were prospectively enrolled between January and June 1995. Data on donors and recipients before and after transplant were collected and included age, gender, alanine aminotransferase (ALT), hepatitis B (HBV), and hepatitis C virus (HCV) markers, hematological disease, status and type of BMT, conditioning regimen and graft versus host disease prophylaxis. Statistical analysis included univariate descriptive and multivariate analysis based on logistic regression on major end-points. RESULTS: Forty-three of 193 patients died during the study period, and liver disease was the main cause of death (13 of 43, 30%). Incidence of severe veno occlusive disease was 8%, fulminant hepatic failure 0.5% and 12% of cases had ALT >500 U/L (normal < or =42 U/L). A de novo HBV or HCV infection occurred in 3.2 and 7% of patients respectively. Predictive risk factors for life-threatening liver disease were: unrelated donors (relative risk=5.8, confidence interval=1.7-19.8) and abnormal BMT donor ALT (relative risk=6.3, confidence interval=1. 5- 25.5). CONCLUSIONS: This study indicates that ongoing or previous infection with HBV or HCV in donor or recipient is not an absolute contraindication for BMT. However, abnormal ALT levels in BMT donors were a significant predictor of potentially lethal liver complications. The occurrence of de novo HBV or HCV infection did not correlate with severity of liver disease observed in the first 6 months posttransplant. These findings should be carefully evaluated before disregarding HBV or HCV positive siblings with normal transaminase levels in favor of unrelated donors.

Hepatitis C virus infection in patients undergoing allogeneic bone marrow transplantation.

Antibody to the recently identified hepatitis C virus was investigated in sera of 128 patients treated with allogeneic bone marrow transplantation, to determine the prevalence of HCV infection and its role in post-transplant liver complications. The overall prevalence of anti-HCV positivity was 28.6% (38/128 patients). The presence of pretransplant anti-HCV positivity (in 10/35 tested patients) did not seem to predict a more severe liver disease. In fact 8/10 anti-HCV+ and 15/25 anti-HCV- patients had elevated transaminases at BMT, and posttransplant liver failure (due to VOD or subacute hepatitis), and post-BMT rises in transaminases occurred regardless of anti-HCV serology (P = 0.6 and 0.2, respectively). In patients tested for anti-HCV after BMT (n = 128), only two (one anti-HCV+ and one anti-HCV-) experienced VOD; the number of patients in whom liver failure contributed to death was comparable in anti-HCV-positive and anti-HCV- negative patients (P = 0.4). Among 17 patients with documented posttransplant seroconversion (from anti-HCV- to anti-HCV+) the appearance of anti-HCV was concomitant with hepatitis exacerbation in 9 (53%). Histologic changes demonstrated a more severe liver damage in anti-HCV+ patients: a chronic hepatitis was diagnosed in 9/11 anti-HCV+ versus 1/7 anti-HCV- cases. Based on these observations, we conclude that hepatitis C virus has a role in liver disease in such patients, although its evaluation by the anti-HCV test is still of limited accuracy, due to low sensitivity and incomplete specificity.

How important is hepatitis C virus (HCV)-infection in persons with acute leukemia?

Hepatitis C virus (HCV)-infection is common in persons with leukemia. Blood transfusions are the typical source and HCV-related chronic hepatitis a common outcome. Development of HCV-infection and -related hepatitis raises important questions about subsequent leukemia treatment including the natural history of the infection and need for treatment modification. Although the natural history of HCV-infection and -related hepatitis in this setting is unknown, data from normal persons with HCV-infection suggest that short-term survival is not likely to be decreased in persons with leukemia and these complications. In contrast, long-term survival may decrease because of a high rate of chronic hepatitis, cirrhosis, and possibly hepatocellular carcinoma. There are no convincing data that HCV-infection or -related hepatitis or alterations in anti-leukemia drug dose or schedule prompted by abnormal liver function tests, alter leukemia outcome. Consequently, it is uncertain whether drug doses and/or schedule should be modified in persons with leukemia and HCV-infection or -related hepatitis. Short-term outcome of blood cell and bone marrow transplants is also unaffected by HCV-infection or -related hepatitis.

Infections with hepatotropic viruses in children treated with allogeneic bone marrow transplantation.

Patients treated with BMT are extremely susceptible to infection with blood-borne viruses that can cause liver disease of variable clinical severity, from minimal biochemical changes to fulminant hepatic failure. Facing a patient with liver disfunction after BMT, one must bear in mind that more than one cause of liver disease, of viral and/or non-viral origin, may coexist. Moreover, besides the most important hepatotropic viruses, other agents, like herpesviruses (including CMV, adenoviruses, Epstein-Barr virus) may also be implicated, sometimes causing a life-threatening fulminant hepatitis, due to their cytopatic effect. Liver disease history and viral markers before transplant, together with the accurate assessment of the timing and type of clinical and biochemical deterioration are useful tools for a differential diagnosis. Liver biopsy, if taken in the early posttransplant period, is often difficult to interpret, while in case of liver disease occurring during immunosuppression tapering, histologic examination may discriminate between an exacerbation of viral hepatitis and an acute onset of chronic liver GVHD. While it seems that hepatitis G virus does not cause liver disease, the presence of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection is a matter of concern for its consequences both early after BMT and for long-term survivors. Despite screening for blood and marrow donors for HBV and, more recently, for HCV markers, the rate of post-transplant infection (4% and 4-15% respectively, confirmed in prospective studies) with those viruses indicates that viral hepatitis still remains an important clinical problem in this setting, although the prognosis of chronic HCV and HBV infection appears more benign than expected, especially in children.

Hepatitis C virus infection and liver disease in children with thalassemia.

Antibody to the recently identified HCV and type of liver disease were investigated in 25 children with homozygous beta thalassemia. All patients were tested at regular intervals by second generation ORTHO-ELISA test. 19/25 (76%) patients were found repeatedly positive: in 11 cases seroconversion from anti-HCV- to anti-HCV+ status could be also documented. Liver disease was more severe in anti-HCV positive children. Seroconversion however did not produce major changes in liver disease outcome.