Therapy-related myelodysplastic syndromes deserve specific diagnostic sub-classification and risk-stratification-an approach to classification of patients with t-MDS.

In the current World Health Organization (WHO)-classification, therapy-related myelodysplastic syndromes (t-MDS) are categorized together with therapy-related acute myeloid leukemia (AML) and t-myelodysplastic/myeloproliferative neoplasms into one subgroup independent of morphologic or prognostic features. Analyzing data of 2087 t-MDS patients from different international MDS groups to evaluate classification and prognostication tools we found that applying the WHO classification for p-MDS successfully predicts time to transformation and survival (both p < 0.001). The results regarding carefully reviewed cytogenetic data, classifications, and prognostic scores confirmed that t-MDS are similarly heterogeneous as p-MDS and therefore deserve the same careful differentiation regarding risk. As reference, these results were compared with 4593 primary MDS (p-MDS) patients represented in the International Working Group for Prognosis in MDS database (IWG-PM). Although a less favorable clinical outcome occurred in each t-MDS subset compared with p-MDS subgroups, FAB and WHO-classification, IPSS-R, and WPSS-R separated t-MDS patients into differing risk groups effectively, indicating that all established risk factors for p-MDS maintained relevance in t-MDS, with cytogenetic features having enhanced predictive power. These data strongly argue to classify t-MDS as a separate entity distinct from other WHO-classified t-myeloid neoplasms, which would enhance treatment decisions and facilitate the inclusion of t-MDS patients into clinical studies.

Salvage chemotherapy with alternating MINE-ESHAP regimen in relapsed or refractory Hodgkin's lymphoma followed by autologous stem-cell transplantation.

BACKGROUND: High-dose chemotherapy (HDT) followed by autologous stem-cell transplantation (ASCT) is considered the gold standard in the treatment of patients with relapsed or refractory Hodgkin's lymphoma (HL). However, the optimal salvage regimen has not yet been established. PATIENTS AND METHODS: We retrospectively analyzed the efficacy and toxicity of MINE (mesna, ifosfamide, mitoxantrone, and etoposide) alternated with ESHAP (etoposide, methylprednisolone, high-dose cytarabine, and cisplatin) in the treatment of 61 relapsed or refractory HL patients after ABVD-based chemotherapy. RESULTS: Overall, 25 patients (41%) achieved a complete response (CR), 23 (38%) a partial response (PR), 4 (7%) a stable disease, and 8 (13%) progressed for an overall response rate of 79%. Response to first-line chemotherapy was the most important prognostic factor for response to MINE-ESHAP (P = 0.041). No grade 4 extrahematologic toxic effects or toxic deaths were observed. Adequate peripheral blood stem-cell collection was achieved in 56 of 59 (95%) mobilized patients. Overall survival and event-free survival after HDT and ASCT were significantly higher for patients achieving CR/PR in comparison with those refractory to MINE-ESHAP (46% and 35% versus 74% and 69%, respectively). CONCLUSION: MINE-ESHAP results in a high response rate with acceptable toxicity in patients with HL having failed ABVD-based treatment.

Cell-cell interaction in erythropoiesis. Role of human monocytes.

Erythroid burst forming units (BFU-E) are proliferative cells present in peripheral blood and bone marrow which may be precursors of the erythroid colony forming cell found in the bone marrow. To examine the possible role of monocyte-macrophages in the modulation of erythropoiesis, the effect of monocytes on peripheral blood BFU-E proliferation in response to erythropoietin was investigated in the plasma clot culture system. Peripheral blood mononuclear cells from normal human donors were separated into four fractions. Fraction-I cells were obtained from the interface of Ficoll-Hypaque gradients (20-30% monocytes; 60-80% lymphocytes); fraction-II cells were fraction-I cells that were nonadherent to plastic (2-10% monocytes; 90-98% lymphocytes); fraction-III cells were obtained by incubation of fraction-II cells with carbonyl iron followed by Ficoll-Hypaque centrifugation (>99% lymphocytes); and fraction-IV cells represented the adherent population of fraction-II cells released from the plastic by lidocaine (>95% monocytes). When cells from these fractions were cultured in the presence of erythropoietin, the number of BFU-E-derived colonies was inversely proportional to the number of monocytes present (r = -0.96, P < 0.001). The suppressive effect of monocytes on BFU-E proliferation was confirmed by admixing autologous purified monocytes (fraction-IV cells) with fraction-III cells. Monocyte concentrations of >/=20% completely suppressed BFU-E activity. Reduction in the number of plated BFU-E by monocyte dilution could not account for these findings: a 15% reduction in the number of fraction-III cells plated resulted in only a 15% reduction in colony formation. These results indicate that monocyte-macrophages may play a significant role in the regulation of erythropoiesis and be involved in the pathogenesis of the hypoproliferative anemias associated with infection and certain neoplasia in which increased monocyte activity and monopoiesis also occur.

Importance of radiotherapy in the outcome of patients with primary CNS lymphoma: an analysis of the CHOD/BVAM regimen followed by two different radiotherapy treatments.

PURPOSE: To assess the effect of a reduced dose of radiotherapy (RT) in patients with primary CNS lymphoma (PCNSL) responding to the cyclophosphamide, doxorubicin, vincristine, and dexamethasone (CHOD)/carmustine, vincristine, methotrexate, and cytarabine (BVAM) regimen. PATIENTS AND METHODS: Patients received one cycle of CHOD and two of BVAM. In the first trial, all 31 patients received 45-Gy whole-brain RT (CHOD/BVAM I). In the second, with 26 patients, RT dose was reduced to 30.6 Gy if there was a complete response (CR) after chemotherapy (CHOD/BVAM II). RESULTS: Age, performance status, and chemotherapy received were similar in both protocols. CR rate at the end of all treatment was 68% for CHOD/BVAM I and 77% and for CHOD/BVAM II. Treatment modality was the only predictor of relapse, with 3-year relapse risks of 29% and 70% for CHOD/BVAM I and II, respectively. This was specifically important in the 25 patients less than 60 years old (3-year relapse risk, 25% v 83%; P =.01). The 5-year overall survival (OS) was 36%. Age (< 60 v > or = 60 years) was the only predictor for OS in the multivariate analysis (relative risk, 2.1; 95% confidence interval, 1.4 to 2.8). RT dose was the only predictor of OS in patients younger than 60 years old who achieved CR at the end of all treatment (3-year OS, 92% v 60% for patients receiving 45 or 30.6 Gy, respectively; P =.04). CONCLUSION: Reduction of the RT dose from 45 Gy to 30.6 Gy in patients younger than 60 years old with PCNSL who achieved CR resulted in an increased risk of relapse and lower OS.

Mesenteric hyaline plasma cell lymph node hyperplasia with amyloid deposits.

Lymph node hyperplasia (mixed hyaline vascular and plasma cell type) of mesenteric localization in a young woman was accompanied by noticeable systemic manifestations--fever, highly increased sedimentation rate, anemia, and hypergammaglobulinemia--that disappeared after the tumor was removed. Perivascular deposits of amyloid material were found within the tumor and in the spleen. To our knowledge, this finding has not been previously reported. On the basis of earlier studies in the literature and other considerations, an immunologic disorder is proposed as the cause of both the general symptoms and the amyloid deposits.

Human peripheral blood erythroid burst forming unit (BFU(E)): evidence against T-lymphocyte requirement for proliferation in vitro.

Erythroid burst-forming units (BFU(E)) are proliferative cells which may be precursors of the erythroid colony-forming unit (CFU(E)). To examine the role of T lymphocytes in the proliferation and/or differentiation of human blood BFU(E), the effect of purified T lymphocytes on erythroid colony (EC) formation by purified null cells was examined in vitro. Lymphocyte subpopulations were prepared by Ficoll-Hypaque centrifugation, immunoadsorbent chromatography, and sheep red blood cell rosetting after removal of monocytes by adherence to plastic. Cultures of isolated B, T, or null lymphocytes alone revealed that BFU(E) were present in the null cell fraction. Addition of isolated B and/or T lymphocytes in various ratios to null cells failed to influence the number or size of EC formed. These results indicate that normal human circulating BFU(E) are contained in the null cell fraction of peripheral blood lymphocytes and do not require T lymphocytes for normal growth and differentiation in vitro.

Effectiveness of azacitidine in unselected high-risk myelodysplastic syndromes: results from the Spanish registry.

The benefit of azacitidine treatment in survival of high-risk myelodysplastic syndromes (MDS) patients compared with conventional care treatment (CCT) has not been established outside clinical trials. To assess its effectiveness, we compared overall survival (OS) between azacitidine and conventional treatment (CCT) in high-risk MDS patients, excluding those undergoing stem cell transplantation, submitted to the Spanish MDS registry from 2000 to 2013. Several Cox regression and competing risk models, considering azacitidine as a time-dependent covariate, were used to assess survival and acute myeloblastic leukemia (AML) progression. Among 821 patients included, 251 received azacitidine. Median survival was 13.4 (11.8-16) months for azacitidine-treated patients and 12.2 (11-14.1) for patients under CCT (P=0.41). In a multivariate model, age, International prognostic scoring system and lactate dehydrogenase were predictors of OS whereas azacitidine was not (adjusted odds ratio 1.08, 95% confidence interval 0.86-1.35, P=0.49). However, in patients with chromosome 7 abnormalities, a trend toward a better survival was observed in azacitidine-treated patients (median survival 13.3 (11-18) months) compared with CCT (median survival 8.6 (5-10.4) months, P=0.08). In conclusion, our data show that, in spite of a widespread use of azacitidine, there is a lack of improvement in survival over the years. Identification of predicting factors of response and survival is mandatory.

Ovarian dermoid cyst-associated autoimmune hemolytic anemia: a case report with emphasis on pathogenic mechanisms.

Autoimmune hemolytic anemia (AIHA) as a manifestation of ovarian dermoid cyst (ODC) is a rare paraneoplastic syndrome of unknown pathogenesis. Among mechanisms postulated to explain this association, cross-reactivity between cyst and red blood cell (RBC) antigens, and local production of RBC autoantibodies by intracyst B lymphocytes are the most likely. Studies to test these hypothesis were done in a patient diagnosed of AIHA associated with a nonpalpable ODC, in whom the AIHA subsided after tumor excision. The RBC-bound autoantibody was an IgG directed against the Rh complex. The cyst's fluid content lacked detectable RBC autoantibodies or immunoglobulins, the latter being measured by a high-sensitivity assay. It also failed to inhibit the ability of the purified autoantibody to agglutinate RBCs. Ovarian dermoid cyst histology disclosed that (1) the biotin-labelled RBC autoantibody did not bind to ODC structures; (2) scanty amounts of small mature lymphocytes (50% CD45RO+; 50% CD20+) were present only in a few tissue sections; (3) plasma cells producing IgM or IgG were extremely scarce; and (4) deposits of immunoglobulins were not detected into the ODC. These data fail to support any of the aforementioned hypotheses on the pathogenesis of this paraneoplastic syndrome. Other possible mechanisms are discussed, and a wider use of imaging diagnosis to search for ODC in women with AIHA is emphasized.

Secondary (AA) amyloidosis associated with Castleman's disease. Report of two cases and review of the literature.

This article describes two patients with localized Castleman's disease (CD) of the mixed hyaline vascular and plasma cell type located at the mesentery of the small bowel, associated with systemic symptoms, anemia, an increased plasma level of acute phase reactants, and systemic amyloidosis. There were amyloid deposits on the vascular walls of the liver, spleen, and mesenteric lymphoid mass. On immunohistochemical studies, amyloid was shown to be of the AA type in both cases. After surgical resection of the mesenteric mass, clinical and laboratory manifestations improved, and the amyloidosis showed no progression in these patients 23 years and 1 year later. The authors' review of the literature shows a striking similarity of CD cases associated with amyloidosis in terms of the abdominal localization of the lymphoid mass, secondary pattern (AA type) of amyloidosis, and improvement of clinical manifestations after removal of the tumor, without progression of amyloid deposition.

Pyoderma gangrenosum triggered by alpha2b-interferon in a patient with chronic granulocytic leukemia.

Pyoderma gangrenosum is a neutrophilic dermatosis that is frequently associated with malignancies such as myeloproliferative disorders. The development of this dermatologic disorder is thought to be mediated by immunological mechanisms. A case of pyoderma gangrenosum associated with the administration of alpha2b-interferon (alpha2b-IFN) in a patient with chronic granulocytic leukemia is described. Discontinuation of alpha2b-IFN and the administration of cyclosporin A and prednisone resulted in cure of the pyoderma gangrenosum. Serum levels of tumor necrosis factor, interleukin-6 and soluble interleukin-2 receptor increased when the cutaneous lesions appeared and returned to normal levels when the lesion healed. We believe that this is the first reported case of pyoderma gangrenosum associated with alpha2b-IFN therapy.

[Systemic chronic candidiasis following typhlitis caused by Candida albicans]. / Candidiasis crónica sistémica después de una tiflitis por Candida albicans.

Typhlitis is an infrequent infectious complication which may appear during a period of intense granulocytopenia, generally in patients with acute leukemia. The most common causal germs are Gram negative bacilli although the importance of Candida sp. as an etiologic agent of this disease is ever more frequent. The case of a 14 years old patient with acute lymphoblastic leukemia who, after chemotherapy treatment, presented typhlitis by Candida albicans followed by chronic systemic candidiasis (CSC) is described. The role that Candida albicans may play in some cases of typhlitis is discussed as is the relation between the appearance of typhlitis and the posterior development of CSC.

[Malignant lymphomas (non-Hodgkin's lymphomas and Hodgkin's disease) associated with infection by the human immunodeficiency virus. Study of 9 cases]. / Linfomas malignos (no hodgkinianos y enfermedad de Hodgkin) asociados a la infección por el virus de la immunodeficiencia humana. Estudio de nueve casos.

Six cases of non-Hodgkin's lymphoma and three of Hodgkin's disease in patients carrying antibodies against human immunodeficiency virus are reported. Mean age was 30.6 years (SD: 6). From the patients with non-Hodgkin's lymphoma, three were homosexual and three were parenteral drug users. The three patients with Hodgkin's disease were parenteral drug users. The primary features of the patients with non-Hodgkin's lymphoma were: degree of malignity intermediate (three patients) or high (three patients), initial extralymphatic involvement (five patients) and advanced stages (IIIA one patient, and IVB four patients). In turn, the patients with Hodgkin's disease presented the following histopathologic varieties: mixed cellularity (two cases) and lymphocytic depletion (one case); advanced stage (III two cases and IV one case) and B symptoms. We wish to emphasize the necessity of determining the existence of antibodies against human immunodeficiency virus in all patients with Hodgkin's disease or non-Hodgkin's lymphomas with high degree of malignity and extralymphatic involvement. In patients with antibodies against the human immunodeficiency virus who present a marked impairment of general condition and/or changes in the clinical features of their adenopathies, the development of a lymphoma must be ruled out.

[Chronic lymphoid leukemia. Survival in relation to clinical stages. Statistical analysis of 95 cases (author's transl)]. / Sobrevivencia de la leucemia linfoide crónica en relación con los estadios clínicos. Análisis estadístico de 95 casos.

The prognosis of patients with chronic lymphocytic leukemia is very difficult to evaluate. The classification system by stages, which at the present time is the most simple and useful method for the prognosis of this disease, recognizes five degrees of involvement: stage 0 (medullary and peripheral lymphocytosis); stage I (lymphocytosis + enlarged lymph nodes); stage II (lymphocyosis + hepato-and/or splenomegaly); stage III (lymphocytosis + anemia), and stage IV (lymphocytosis + thrombocytopenia). In the present report 95 controlled patients at the Farreras Valentí School of Hematology are analyzed using the classification by stages; there were 19 cases in stage 0; 16 in stage I; 30 in stage II; 21 in stage III, and 9 in stage IV. The mean survival rate in the global series was 63 months and the average 90.9 months. As in other series, it was observed that patients in stages 0 and I have a much better prognosis than those in stages III and IV. Stage II occupies an intermediate position in relation to prognosis, since the actuarial survival figure for this stage can practically be superimposed on that of the global series. The classification of chronic lymphocytic leukemia by stages permits the specification of the therapeutic indications for this condition; it also encourages the search for new modalities of treatment for stages with poor prognosis, since in these cases chronic lymphocytic leukemia behaves in the manner of an acute or subacute hemopathy.

[Sepsis caused by Candida parapsilosis. Joint and lung involvement in 2 patients with acute leukemia]. / Sepsis por Candida parapsilosis. Afección articular y pulmonar en dos pacientes con leucemia aguda.

Sepsis due to Candida parapsilosis with involvement of the joints and the lungs, respectively, is reported in two patients with acute leukemia. The first patient had ankle arthritis 72 days after an allogenic bone marrow transplant for acute lymphoblastic leukemia. The second patient had pneumonia with cavitation during pancytopenia after chemotherapy for acute monocytic leukemia. In both cases, C. parapsilosis sepsis responded to therapy with amphotericin B, associated with miconazole in the first patient and with 5-fluorocytosine in the second one. The rarity of septic foci during C. parapsilosis fungemia and the good outcome of both patients are emphasized. This good result was probably due to early antifungal therapy and the relatively rapid recovery of granulocytopenia.

[Laparoscopic splenectomy as an alternative to open surgery in the treatment of autoimmune thrombocytopenia]. / La esplenectomía laparoscópica como alternativa a la intervención quirúrgica convencional en el tratamiento de las plaquetopenias de origen autoinmune.

BACKGROUND: Several studies have shown the potential advantages laparoscopic splenectomy (LS) over open surgery. The aim of this study has been to evaluate the advantages of LS over open surgery in the treatment of autoimmune thrombocytopenia. PATIENTS AND METHODS: 54 consecutive patients splenectomized for the treatment of idiopathic thrombocytopenic purpura (ITP) or HIV-related thrombocytopenia were analyzed. Operative features (operative time, conversion to open surgery, accessory spleens), immediate (stay, analgesia and blood transfusion requirements) and late postoperative features (platelet count), as well as splenectomy-related complications in both surgical procedures were compared. RESULTS: Between February 1990 and February 1997, 54 splenctomies were performed for the treatment of autoimmune thrombocytopenia (ITP, n = 47, and HIV-related thrombocytopenia, n = 7). Eighteen were performed through an open approach, and 36 by laparoscopy. Both groups were comparable with regard to age, sex, platelet count, disease duration and body mass index. LS was completed in 34 cases (conversion to open surgery: 5.5%). The incidence of accessory spleens was 11% in the LS group and 5.5% in the open surgery group. Postoperative morbidity (16% vs 28%) and blood requirements (25% vs 33%) were lower after LS, but the differences did not reach statistical significance. Analgesia requirements (7 [SD 3] vs 11 [6]; p < 0.01) and postoperative stay (3.8 [2.6] vs 7.4 [3] days; p < 0.01) were significantly shorter after LS. Following splenectomy, the platelet counts became normal in 72% of patients submitted to LS and 78% of patients in the open surgery group. After 20 and 63 months mean follow-up, one patient in each group developed late complications. CONCLUSION: As compared to open surgery, LS offers a better immediate clinical outcome, with similar long-term results.

[Molecular study of red cell pyruvate kinase deficiency in 15 patients with chronic hemolytic anemia. Group of Erythropathology of Hematology and hemotherapy Association of Spain (HHAS)]. / Estudio molecular del déficit de piruvatocinasa eritrocitaria en 15 pacientes con anemia hemolítica crónica. Grupo de Eritropatología de la Asociación Española de Hematología y Hemoterapia (AEHH).

BACKGROUND: Identification of RBC pyruvate-kinase (PK) gene mutations by polymerase chain reaction (PCR) and single strand conformation polymorphism (SSCP) followed by PK gene sequencing in positive cases has been assessed and the results obtained with a preliminary study of 15 unrelated patients of Spanish origin are presented. PATIENTS AND METHODS: Patients have been classified into two different groups: group 1, propositus (15 cases), and group 2, relatives of the patients included in group 1 (10 males and 5 females). In group 1, a PCR was followed by SSCP and sequencing, and in group 2, the PCR was followed by digestion with specific restriction endonucleases (PCR-ER). RESULTS: Group 1: from 15 patients included in the study 2 were identified as homozygous, 4 as heterozygous and 9 as compound heterozygous. In this group, were identify 26 affected alleles with 11 different mutations: T1456 10 alleles (38.6%), T721 3 alleles (11.6%), A1010, C514, C1015 and T1223 2 alleles (7.7%), and C1070, A1291, T1508, A1595 y T1675 one allele. Relatives from 8 out of 15 patients from group 1 showed the following pattern: homozygous (one case), heterozygous (10 cases), compound heterozygous (2 cases) and normal (2 cases). CONCLUSIONS: SSCP procedure followed by direct gene sequencing in positive cases is fast and simple enough to allow the identification of PK deficient variants, avoiding the need of biochemical characterisation of semipurified deficient enzyme, which is more cumbersome and time consuming. In addition, the PCR-ER method is a very useful tool for screening of the most frequent molecular variants, as well as, for the detection of the carrier condition of this enzymopathy (family studies).

[Hemopoietic progenitor cell transplantation: 20 years' experience at the Hematology School "Farreras-Valentí"/Clinical Hospital of Barcelona]. / Trasplante de progenitores hemopoyéticos: 20 años de experiencia en la Escuela de Hematología "Farreras-Valentí"/Hospital Clínic de Barcelona.

BACKGROUND: Hemopoietic progenitor cell transplantation (HPCT) is acquiring an increasing role in the therapy for a variety of disorders. In this study, main characteristics and results of HPCT along 20 years are analyzed from the experience of Postgraduate School of Hematology "Farreras-Valentí" at the Hospital Clínic in Barcelona. PATIENTS AND METHODS: Six-hundred ninety-five patients transplanted between June 1976 and January 1996 were analyzed. Median age (range) were 33 (4-63) years. The following aspects were considered: donor type, source or progenitor cells, type of disease and disease-stage at transplantation, transplant related mortality and survival. RESULTS: A total of 714 HPCT were performed (448 allogeneic, 13 isogeneic, 253 autogeneic). Allogeneic HPCT were from an HLA-identical sibling in 408 cases, from other familial donors in 10, and from non-familial donors in 30. Most HPCT from non-familial donors (93%) were performed during the last five years of the study (1991-1995). The source of hemopoietic progenitor cells was bone marrow in 625 instances (88%), peripheral blood in 88 (12%), and fetal liver in one. During more than 15 years, the only source of progenitors was the bone marrow; in contrast, in the last 3 years (1993-1995) transplants using peripheral blood were predominant. Main indications for HPCT were the following: acute leukemias (n = 387) (54%), chronic leukemias (n = 134) (19%), severe aplastic anemia (n = 58) (8%), lymphomas (n = 80) (11%), multiple myeloma (n = 39) (5%) and myelodysplastic syndromes (n = 14) (2%). In patients with hematological malignancies (n = 656), HPCT was performed in first complete remission or in first chronic phase in 321 instances (49%), in subsequent remissions in 144 (22%), and in more advanced stages in the remaining 191 (29%). In the more recent years, a progressive decrease in the number of HPCT for acute leukemia or aplastic anemia was observed, contrasting with an increase in transplants for lymphoma, multiple myeloma and myelodysplastic syndromes. Of note, a significant decrease in transplant related mortality was evident along the years, both after autogeneic HPCT (21% during 1985-1992 and 6% thereafter) (p = 0.001) and after allogeneic transplantation (54%, 44%, and 20% during the periods 1976-1984, 1985-1992 and 1993-1995, respectively) (p = 0.004). The fact translated into an increase in the actuarial probability of survival after allogeneic HPCT (25%, 33% and 58% in the three mentioned periods, respectively) (p = 0.0003), and after autogeneic HPCT (33% in the interim 1985-1992, and 55% in the period 1993-1995) (p = 0.001). CONCLUSIONS: During the last 20 years, HPCT has significantly evolved in aspects such as type of donor, source of progenitor cells and indications. Remarkably, a progressive decrease in transplant related mortality has been observed translating into a improvement in survival after the procedure.

Effect of glucocorticoid treatment on Wnt signalling antagonists (sclerostin and Dkk-1) and their relationship with bone turnover.

The aim of this study was to analyse the effect of glucocorticoid therapy (GCCT) on Wnt signalling antagonists (sclerostin and Dkk-1) and their relationship with bone turnover. 25 patients (8 M/17 F, aged 48±19yrs) recently initiating GCCT (≥7.5mg/day, ≤6months) were prospectively included. Bone turnover markers (bone formation: P1NP, osteocalcin [OC], bone ALP; bone resorption: sCTx) and Wnt antagonists (serum sclerostin and Dkk-1) were assessed in all patients (short-term and 12months after initiating GCCT). Bone mineral density (BMD) was performed to assess osteoporosis. The results were compared with 60 healthy controls. At short-term patients on GCCT showed a significant decrease in bone formation markers versus controls (P1NP: 19±9 vs. 43±16ng/mL, p<0.001; OC: 7.4±2.4 vs. 18.4±5.2ng/mL, p=0.001) and in Dkk-1 levels (24.5±20.1 vs. 36.8±13.7pmol/L, p=0.008) with similar sclerostin values (41.8±21.8 vs. 42.1±13.9pmol/L, p=0.950). Sclerostin correlated positively with GCCT doses (r=0.449, p=0.024) and lumbar BMD (r=0.424, p=0.035), and negatively with bone ALP (r=-0.398, p=0.049). A progressive decrease in Dkk-1 levels was observed at 12months, (19.1±14.9, p=0.001), whereas sclerostin increased compared to controls (48.9±11.6, p=0.045). In conclusion, the effect of GCCT on the serum levels of the Wnt signalling parameters differs depending on the antagonist evaluated. Whereas sclerostin values increased and showed a relationship with the dose and bone AP, Dkk-1 levels decreased throughout the study suggesting a counter-regulatory mechanism of this factor thereby reducing the deleterious effect of GCCT in the bone.

The degree of neutropenia has a prognostic impact in low risk myelodysplastic syndrome.

The severity of neutropenia in myelodysplastic syndrome (MDS) has not been completely studied. We analyzed the prognostic significance of severe neutropenia (neutrophils count <0.5×10(9)/L) at diagnosis in 1109 patients with de novo MDS and low/intermediate-1 IPSS included in the Spanish MDS Registry. Severe neutropenia was present at diagnosis in 48 of 1109 (4%). Patients with severe neutropenia were most strongly represented within the groups of refractory cytopenia with multilineage dysplasia (40%) and refractory anemia with excess of blast type 1 (29%). Severe neutropenia had negative effects on the low/intermediate-1 risk group. A significant difference in overall survival was observed between patients with severe neutropenia (28 months) and patients with a neutrophil count higher than 0.5×10(9)/L (66 months) (p<0.0001). Also, severe neutropenia predicted a significantly reduced on leukemia-free survival (p<0.0001). In the multivariate analysis, severe neutropenia retained its independent prognostic influence on overall survival [HR: 2.19, 95% CI (1.41-3.10), p<0.0001] and leukemia free survival [HR: 3.51, 95% CI (1.97-6.26), p<0.0001]. The degree of neutropenia should be considered as additional prognostic factor in low/intermediate-1 IPSS MDS.