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To the Editor: We read with interest the report by Kawano et al[1][1]concerning the use of granulocyte colony-stimulating factor (G-CSF) after peripheral blood stem cell transplantation (PBSC) in pediatric patients. The main conclusions of this study are that filgrastim does not provide a marked

Background: Chronic lymphocytic leukemia (CLL) has an extremely variable clinical course. Some patients have a rapid and fatal evolution, and die earlier after diagnosis, whereas others have an indolent disease, and live for 10–20 years without symptoms. Ray and Binet system have been classically considered standard clinical staging method, but have a recognised limitation to identify the real risk to start treatment in patients with initial stage of disease (Rai 0–2, Binet A). Objetive: Our objective was to evaluate the impact of biological variables (cytogenetic analyses and CD38 and ZAP70 expression) independently of Rai and Binet stage at diagnosis, in the need of treatment. Moreover we analyzed the treatment-free survival at 12 and 60 months. Patients and methods: Our study includes 347 patients with B-CLL, 167 men and 180 women, with a median age of 70 years (range 35–97 years) who were retrospectively analyzed. All patients were diagnosed in our center during a period of 20 years, on the basis of a clinical examination as well as morphological and immunological criteria. Chromosomal abnormalities were studied using FISH cytogenetic methodology in 79.3% of patients. Patients with normal karyotype or single abnormality of 13q-, were considered in the group of favourable prognosis. Patients with other abnormalities such as trisomy 12, 17p- and 11q-, were considered as high risk of progression. CD38 expression was analyzed by flow cytometry in 90.2% of patients. A cut-off ≥30% was defined to distinguish positive and negative expression. ZAP70 expression was studied in 64.8% and we considered positive a cut-off ≥20%. Results: 78.9% of patients were classified by FISH in the good risk prognosis group. CD38 positive expression was detected in the 24.6% and ZAP70 was positive in the 56%. When we analysed the biological characteristics of treated patients we observed that they expressed CD38, ZAP70 and unfavourable karyotype more frequently than total population studied. These differences were more significant than the relationship with Rai and Binet stage. At 12 months of follow-up, we found that only 21% of patients with CD38 negative expression need treatment versus 40% of patients with positive expression. 25% of patients with ZAP-70 negative expression and 35% of ZAP-70 positive expression need treatment at this moment. 27% of patients with favourable kariotype and 29% of patients with unfavourable cytogenetic were treated (Figure 1). At 5 years since the moment of diagnostic, these differences were more significant. 82% of patients with CD38 positive expression need treatment versus 64% of patients with CD38 negative expression; 80% of patients with unfavourable cytogenetic need treatment versus 64% of patients with favourable kariotype. No differences were found in the two groups of the ZAP70 expression (Figure 1). Conclusions: We observed that biological markers, fundamentally CD38 expression, predict need of treatment. The percentage of treated patients was significantly higher in the group of CD38 positive expression at the moment of diagnosis. The follow-up of our patients shows that the treatment-free survival is lower in patients with CD38 positive expression, so this marker could be used to predict need of treatment and separate those cases of smouldering B-CLL that no need to be observed so intensively in which the best option of treatment is “watch and wait”. Figure 1. Treatment-free survival in 347 patients with B-CLL according to karyotype, CD38 and ZAP70 expression. Figure 1. Treatment-free survival in 347 patients with B-CLL according to karyotype, CD38 and ZAP70 expression.

Introduction: The prevalence of hepatitis B virus (HBV) in transplanted patients is not negligible and reactivation of latent HBV infection in the setting of allogeneic HSCT is a well-known complication. However, reverse seroconversion (RS) from positive hepatitis B surface antibody (HBsAb), positive hepatitis B core antibody (HBcAb) and negative hepatitis B surface antigen (HBsAg) to negative HBsAb and positive HBsAg has been less reported. The aims of our study were to describe the clinical characteristics of patients with cured hepatitis B and to identify associated conditions with RS after allogeneic HSCT. Secondarily, we have analyzed the behavior of patient’s serology for HBV after transplantation in relation with donors’ immunity. Materials and methods: From April 1999 to April 2008, we evaluated the outcome regarding HBV serological status and liver function tests abnormalities of patients cured hepatitis B who received allogeneic HSCT. We assessed the presence of liver GVHD, sinusoidal obstruction syndrome, conditioning treatment, subjacent hematological disease and number of infused CD34+ cells as possible variables associated with RS. Data were analyzed with the statistical software SPSS15.0. Chi-Square test, Fisher’s exact test and Mann-Whitney test were used for statistical analysis. Results: Of 107 transplanted patients, we found 24 patients (22.4%) with serology consistent with cured hepatitis B previous to transplant. Median age at transplant was 25 years (range, 16–49). The median follow-up time after transplant was 27 months (range. 2–76). The subjacent hematological disease was acute leukemia in 11 patients, lymphoma in 4, myeloproliferative syndromes in 3, myelodysplastic syndromes in 2, severe aplastic anemia in 2 and multiple myeloma in 2. All patients received myeloablative conditioning. Twenty patients were transplanted from siblings, 3 patients were transplanted from matched unrelated donors and 1 patient received umbilical cord blood progenitor cells. Nineteen patients received peripheral stem cells and 4 patients were infused with bone marrow. The mean number of infused CD34 was 5,18x106/Kg. Eight patients developed liver GVHD confirmed by biopsy. Four patients had sinusoidal obstruction syndrome. Six of the 24 patients (25%) developed RS. All the patients with RS had liver GVHD and acute hepatitis appeared after a mean time of 13.5 months (range, 3–34) after immunosuppressive treatment for GVHD was stopped. The most prevalent hematological disease in patients with RS was acute leukemia (5 of the 6 patients with RS, not significant, p=0.2). Four of the 6 patients with RS died of liver failure. The remaining 2 patients are presently on treatment with entecavir. HBV RS was significantly associated with liver GVHD (p=0.007). No other significant association was found. Three donors were naturally immunized, 12 vaccinated, and 4 not-immunized. Data were missing in 5 donors. Loss of HBcAb and HBsAb was seen in all the three patients transplanted from naturally immunized donors within the year of transplantation. Five of twelve patients (41.6%) transplanted from vaccinated donors maintained immunization during a median follow up time of 40 months. Conclusion: RS is a not minor complication after HSCT in patients with previously cured hepatitis B. To our knowledge, this is the first study that establishes an association between liver GVHD and RS. Immunosuppressive treatment for liver GVHD is possibly implicated in the pathophysiology

Introduction: Candidemia is a serious condition with a high mortality rate in patients with hematological malignancies. It is thus important to understand the associated risk factors, as well as the need to establish adequate prophylaxis and early, effective therapy. The objective of this study was to determine the incidence of candidemia in hospital patients with hematological malignancies; to describe its clinical features and the risk factors associated with infection and with a poor outcome. Materials and methods: An electronic database was used to identify cases with a positive blood culture for Candida spp in patients with hematological malignancies admitted to the Hematology Ward of Hospital Universitario La Paz between January 2000 to March 2008. The clinical history of each identified case was reviewed. SPSS 15.0 was used for the statistical analysis. Univariant analysis was carried out using χ2. Results: Forty seven patients were identified, with an annual incidence of 1%. The species identified were Candida parapsilopsis in 46% of cases (n = 22) and Candida albicans in 21.3% (n = 10); the remainder was distributed amongst C. guillermondi, C. tropicalis and C. krusei. The underlying hemalogic malignancies were non-Hodgkin lymphoma (34%, n = 16), multiple myeloma (19%, n = 9) and acute myeloid leukemia (17%, n = 8). 48.9% of patients underwent stem cell transplantation (45.3% allogeneic and 54.7% autologous). No significant association was found between the underlying hemalogic malignancy and the species of Candida that was isolated. The antifungals used in treatment were liposomal amphotericin in 48.9% of cases, fluconazole in 12.7%, caspofungin in 4.2% and voriconazole in 4.2%, with combined therapy in 30% of patients. MIC50 and MIC90 for fluconazole against C. parapsilopsis were 4 and 32, respectively, and 0.03 and 8, respectively against C. albicans. MIC90 against the other species was 0.03. MIC50 and MIC90 for amphotericin were 0.03 and 1, respectively, against C. albicans, C. parapsilopsis and C. krusei. Voriconazole, itraconazole and caspofungin were found to have an MIC90 of 0.03 against all species of Candida. Thirty seven point eight percet of patients were already receiving antifungal prophylaxis at the time of diagnosis of candidemia, although 90% of cases of C. albicans candidemia were not on prophylaxis (p Conclusion: Candida parapsilopsis was found to be the main causative species of candidemia in our centre, with a markedly high MIC50 and MIC90 for fluconazole, probably related to fluconazole prophylaxis. These findings highlight the importance of understanding the epidemiology of each centre when planning treatment and establishing an effective scheme of prophylaxis in high-risk patients to avoid the mortality associated with this type of infectious complication

BACKGROUND: A review of autoimmune(AI)events(AIE) post- autologus stem cell transplantation(ASCT) has recently been published(Daikeler T et al, 2007) but there are few papers about treatment and outcome of AI thrombocytopenia(IT) due to the low frequency and short follow-up.We have reviewed reported cases of IT because the mechanisms are multiple and poorly understood. METHOD: Patients(29p)had been diagnosed with leukaemia 13p, MM 2p, NHL 10p, MSD 1p or solid tumours 3p.Several transplantation variables have been analysed to find any clinical features related to higher risk of IT. Response to treatment and clinical follow-up have been studied, too. RESULTS: There was no direct relation between gender(58.62% female);age(38,83; range 16–58);WBC(5,68x109/l; range1–19) or source and IT(63x109/l; range:1–279).Contrary to reported cases, fludarabine(FLUD),total body irradiation(ITB) administered as conditioning(13,8%)/mobilization regimen (37,8%) or rhG-CSF treatment(2 p) were not associated to AIE. However, the study has important limitations like FLUD was administered in only 3p and mobilization treatment was similar in all cases(Table).IT was resolved in all patients and recurred in only 1p early since steroid(CE) treatment had been stopped.Treatment was not necessary in 2p.The period between transplant and thrombocytopenia was 23.1 months(range 1–80) so aplasia alone can not explain it and it is obligatory to investigate the role of immune deregulation.Steroid, IVIg, Danazol or monoclonal antibody(Rituximab) are possible treatments. DISCUSSION: Different hypothesis have tried to explain postransplant AIE and most authors conclude that the modification of self-antigens expression or its combining with forming “altered self” antigens might contribute.The radio-chemotherapy damage thymic function and deplete T cells(CD8/CD4) while expanding B cells. However, the mechanism of clonal proliferation of B cell remains unclear.Furthermore, the breakdown of tolerance and delayed(≤6 months) recovery of regulatory T cells after some drugs like FLUD have not been properly explored yet.The bone marrow biopsy is an obligatory diagnosic tool for distinguish between delayed recovery and ITP. However, the anti platelet IgG test is not a major diagnostic criterion(pos 13/26 of total IT) because CE have been usually administered previously. It has positive predictive value(VPP) 46% and VPN 82%. The favourable response of AIE to therapy might support the role of graft-versus-host disease after ASCT. CONCLUSION: Although IT is more unusual, it should be considered in the differential diagnosis of post-transplant thrombocytopenia. Its relationship with antitumoral effect and post-transplant immune reconstitution should be considered for growing development of immunotherapy. Drugs received prior to ASCT in the 29 reported cases. QT N°cases % QT N°cases % Az: Azathioprine;BM: bleomycin; Bu: busulfan; Bz: bortezomid; CLB: chlorambucil; CTX: cyclophosphamide;DXT: dexamethasone; DOX: doxorubicin; Etop: etoposide;IDA: Idarrubicina; IFOS: Ifosfamide; Melph: melphalan; MTX: methotrexate; MTZ: mitoxantrone;6TG: 6-thioguanine; VLB: vinblastine; VCR: vincristine.*QT schedule Bz 2 6,9 VCR 5 17,2 PROMACE* 2 6,9 CE 4 13,8 VLB 2 6,9 m-AMSA 4 13,8 BM 2 6,9 MTZ 4 13,8 MTX 3 10,3 AZA 2 6,9 IFOS 4 13,8 Melp 2 6,9 ACVBP* 4 13,8 Ranimustina 2 6,9 BEAM* 3 10,3 DXT 3 10,3 Cisplatin 3 10,3 Thiotepa 2 6,9 CTX 10 34,5 Carboplatin 2 6,9 BCNU 2 6,9 FLUD 3 10,3 Etop 11 37,9 CHOP* 4 13,8 Bu 2 6,9 TBI 4 13,8 DOX 10 34,5 CLB 2 6,9 ARA-C 12 41,4 NA 6 20,7 6TGN 7 24,1

To the Editor : In a very interesting report, Vicenzi et al[1][1] examine the virologic state of seven individuals with long-term nonprogressors characteristics (LTNPs) selected from a well-characterized cohort of human immunodeficiency virus (HIV) infected hemophiliacs. One of the most important

Introduction: Justification and Objectives There are little epidemiologic data about Myeloma Multiple in Spain. The heterogeneity and complexity of this pathology, and the several sociodemographic factors, justify the interest of this type of studies. On the other hand, this disease needs a high assignement of welfare and therapeutic resources, and besides new strategies have arisen for its treatment. The Spanish Leukaemia and Lymphoma Foundation (FLL)has analyzed the actual situation of Myeloma Multiple in Spain, compiling several epidemiologic and welfare parameters about the disease in a Multiple Myeloma “White Book” for Spain. Patients and Methods The period of analysis was 10 years, from 1.991 to 2.001. The information was compiled from a Hospital Based Survey about MM and the following official sources: International Agency for Research on Cancer (IARC): “Cancer incidence in Five continents” and “Incidence and Mortaliity for Cancer In Spain, Patterns and Tendences” Data Base of EUCAN and GLOBOCAN (Cancer Incidence, Mortality and Prevalence Worldwide) EUROCARE III study, (IARC Cancer Base Number 5, Lyon, IARCPress). “Natural Changes of Population and Demography. Spanish National Statistic Institute (INE) and National Spanish Center for Epidemiology (CNE.) Official Records for Mortality Rates by MM in Spain in Spanish Regions (CCAA) (death records Demograhy Records of INE). INE Hospital Case Rate Inquest. CMBD Data Base of Department of Health (Inmunoproliferative Neoplasm and Multiple Myeloma, CIE-9 Diagnosis Code: 203.0)The indicators used were: Deaths number, median of age, proportional mortality, mortality rates, mortality rates adjusted by age, gender and potential years of life lost due to multiple myeloma, (item 203 of ICD-10, OMS) during the last ten years in Spain. Results The incidence rates of MM, adjusted to the European population were: 3,54 cases by 100.000/year for men and 2,54 cases by 100.000/year for women. The global incidence rate were 4,44 cases by 100.000/year for men and 4,22 cases by 100.000/year for women. These rates were similar in all geographic regions. Performed predictions show a prevalence increase during the following five years, which means more than 2.400 cases in men and more than 2.100 in women MM cases per year. Regarding mortality, rates, myeloma is a very slightly frequent cause of death: 3.23 cases by 100.000/years of men and 2.3 cases of women. A whole an increase of mortality of 45.2 per cent was observed for the period of time between 1992 and 2001. Comments and Conclusions The MM incidence and mortality rates in Spain for this period were lower than expected in comparison with other European epidemiology studies. Nevertheless we observed that the MM mortality and prevalence rates present a continuous and uniform increment in the last years. Part of these increases can be due to the incorporation of new technologies, more sensitive for diagnosis, and to the increase of aging of the population. Furthermore certain occupational and chemical exposures and other environmental changes could explain these trends.

Based on results of GELA study, rituximab in combination with CHOP chemotherapy, given for eight cycles, may be considered the new standard of care for patients older than 60 years diagnosed with DLBCL. However, the afraid of early toxicity and underlying co-morbid illness in elderly patients implies often adjustments in this scheme. The aim of this study was to analyze the routine clinical practice in the up-front treatment of elderly patients (>65 years) with DLBCL. We have enrolled onto this study 80 patients (48 females) with median age 74 years (range, 65 to 85 years) who have been treated with CHOP-like regimens in combination with rituximab as first-line therapy. The 75% of patients had ECOG 0-1, 81% had Ann-Arbor stage III-IV, 41% had B-symptoms, 59% had aIPI 2-3, 39% had bulky disease (> 7 cm) and 55% had elevated beta-2 microglobulin. The most of patients received as up-front therapy R-CHOP (89%); R-CNOP and R-CEOP (doxorubicin is substituted for mitoxantrone and epirubicin, respectively) were the alternative regimens administered. The 57.5% of patients received 6 courses of treatment; the 25% received less than 6 cycles and only the 6% of patients (5 out of 80 patients) received 8 courses of treatment. In 31 out of 80 patients the doses of chemotherapy was reduced; in 20 patients the doses of chemotherapy were reduced in all courses and 2 patients received reduced doses of chemotherapy in 5 out of 6 cycles. In the 40% of patients G-CSF have been administered. The overall response rate was 86% (72% CR/CRu, 14% PR). In the 22 patients who received the lower doses of chemotherapy the overall response rate was 82% (50% CR/CRu) versus 88% in the remaining patients (81% CR/CRu) (p

Background: The mechanism of autoimmunity of chronic idiopathic autoimmune thrombocytopenia (cAITP) is not fully understood but may involve binding of antigenic peptides to HLA antigens. We studied MHC class II phenotypes in adult patients with cAITP. Methods: We have typed 64 adult Caucasian (Spanish) patients with cAITP (17 male and 59 female; median age 47 years range 17–77 years), and compared with the data from to control groups with geographic and ethnic differences. 200 Spanish control samples and 617 American control samples were analyzed. Patients with cAITP were evaluated according to their response to treatment with steroids, splenectomy, dapsona and Anti-CD20. According to the clinical response to the therapy we were able to form two subgroups; patients with good response, normal platelet count during therapy/after splenectomy and poor, less than 50x109/L or no response. Splenectomy was performed in 19 patients and resulted in a bad response in 11 patients of them. 25 of these patients showed a good and 39 a poor response. Class II typing was performed using polymerase chain reaction (PCR) with sequence specific primers. Results: The comparison of antigen frequencies of the whole group of patients with cAITP and the two groups of healthy controls (Spanish and American samples) revealed significant increase of the HLA-DR12 and HLA-DR10 alleles of the MHC class II especifities (p Conclusions: Our data showed that DRB12 and DRB10 were more prevalent in ITP patients than in the two different control groups. Moreover, the difference in the genetic distribution of HLA-DR2 and HLA-DR4 in patients with good and poor response to treatment may indicate that ITP is a more heterogeneous condition than previously suspected, and this genetic marker may improve the early management of patients by better predicting prognosis.