bluuebunny/crossref_metadata_2025_split huggingface dataset:
From megakaryocytes to platelets: platelet morphogenesis takes place in the bloodstream
Authors: Behnke Olav , Forer Arthur 
Published: July 2010

Abstract:We studied megakaryocyte processes formed in rat bone marrow and spleen, using both the transmission and scanning electron microscopes. Some processes were bulky, others slender and beaded. The bulky megakaryocyte processes developed a specialized arrangement of organelles at the site at which they entered the lumen: filaments present around the outside of the process seemed to support a central cylinder in which organelles flowed along microtubules.Megakaryocyte processes were present in platelet‐rich plasma from both human and rat blood. When followed in living preparations, bulky processes developed pointed tips, elongated, and became slender and beaded. Fusiform proplatelets also were present in the platelet rich plasma, with pointed tips at both ends of what appeared to be single “beads”; we assume that the long, beaded megakaryocyte processes would have fragmented were we to have had proper culture conditions.The straight, shorter fusiform proplatelets in living preparations underwent characteristic curving and bending motions, eventually forming disk‐shaped cells which sometimes had appendages. This behaviour suggests that the entire process of platelet morphogenesis takes place in plasma: megakaryocyte processes first elongate, then bead and fragment, and then curve and fuse to form disk‐shaped platelets. This interpretation is strengthened by finding in freshly isolated plasma many of the shapes seen in the transformations studied in living cell preparations.The megakaryocyte processes and the proplatelets seemed to appear in plasma with a periodicity related to light and dark cycles – that is, with a circadian rhythm. In particular, megakaryocyte processes appear in human blood within a few hours after sunrise; we argue that this might be related to similar peak periods for heart attacks.
Arterial elastorrhexis: manifestation of a generalized elastic tissue disorder in β‐thalassaemia major
Authors: Tsomi K. , Karagiorga‐Lagana M. , Fragodimitri C. , Karabatsos F. , Katsiki V. 
Published: July 2010

Abstract: Pseudoxanthoma elasticum‐like lesions of the eye and skin are frequently observed in β‐thalassaemia, and there has been speculation about associated vascular lesions. This led to our study of histopathological material from thalassaemic patients.Histological re‐examination was made of a series of 45 spleens and 45 surgical liver biopsies from 45 patients with β‐thalassaemia major, aged 6–25 yr and treated over the 20‐yr period 1975–95. Correlations between clinical, laboratory and histological findings were demonstrated by statistical analysis.Arteriopathy characterized by fragmentation and multiple defects of the internal elastic lamina (‘arterial elastorrhexis’), with deposits of iron and calcium salts, was found in the hilar arteries of the spleen with a frequency of 96%. Similar lesions were observed in the parenchymal arteries and the stromal elastic tissue (‘stromal elastorrhexis’) of the spleen, liver and lymph nodes. Arterial and elastic tissue alterations appear in the first decade of life and become generalized over the course of the disease, independent of the time of onset of transfusion and iron chelation therapy.Arterial elastorrhexis is the earliest and most frequent manifestation of a systemic elastic tissue disorder in β‐thalassaemia major. It appears to be an acquired pseudoxanthoma elasticum‐like syndrome, related primarily to tissue hypoxia and disturbance of elastin metabolism.
Combination of granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) and erythropoietin (EPO) for the treatment of advanced non‐responsive chronic lymphocytic leukemia
Authors: Russo Filippo , Guadagni Stefano , Mattera Gioacchino , Esposito Giuseppe , Abate Giuseppe 
Published: July 2010

Abstract: We report the use of a colony‐stimulating granulocyte‐macrophage factor (GM/CSF) and erythropoietin (EPO) combination as salvage treatment in four heavily‐pretreated patients with refractory/recurrent B‐CLL. Induction therapy was subcutaneous GM‐CSF 2.5 μg/kg, and EPO, 150 units/kg both daily for the first 14 d. Maintenance therapy was GM‐CSF on days 1, 3 and 5 and Epo on days 2, 4 and 6 at the same doses with weekly recycling. All the patients responded favourably. A significant reduction of lymphocytosis, lymphoadenomegaly, and organomegaly was obtained within one month of therapy. The number of infections and transfusional requirement decreased dramatically. The hemoglobin increased to over 11 g/dl in 3 out of 4 patients. With a median follow‐up of 11 months (range 5–13) we observed 4 partial responses (NCI/IWCLL) and only one progression after a 10‐month partial response.This combination regimen seems very active, safe and easy to administer. It may represent a promising therapeutical option in heavily pretreated patients. Further clinical and biological studies on a larger cohort of patients are needed to confirm these preliminary data, to clarify the hypothetical interactions between these cytokines and B‐CLL cell proliferation pathways, and to establish if this therapy may have an impact on survival.
Response and adverse drug reactions to combination chemotherapy in elderly patients with aggressive non‐Hodgkin's ymphoma: comparison of CHOP, COP‐BLAM, COP‐BLAM III, and THP‐COPBLM
Authors: Niitsu Nozomi , Umeda Masanori 
Published: July 2010

Abstract: We retrospectively compared therapeutic results and adverse events in 198 elderly patients (≥70 yr old) with aggressive non‐Hodgkin's lymphoma diagnosed between 1981 and 1995 who underwent CHOP, COP‐BLAM, COP‐BLAM III, or THP‐COPBLM chemotherapy. Complete remission (CR) was achieved in 138 patients (69.7%). The CR rate was 47.0% for CHOP, 76.3% for COP‐BLAM, 67.9% for COP‐BLAM III, and 74.4% for THP‐COPBLM therapy (p = 0.013). The 5‐yr survival rate was 37.0% for CHOP, 49.0% for COP‐BLAM, and 53.5% for COP‐BLAM III. The event‐free survival rate showed no significant differences between the four treatments. Adverse events of Grade 3 or worse were commonly anemia or granulocytopenia in patients receiving THP‐COPBLM therapy. Cardiac sympathetic dysfunction and cardiac mitochondrial damage were less common with pirarubicin than with doxorubicin.For elderly patients, it is better to select therapy with as few adverse events as possible based on the complications and medical history of the individual patients.
Long‐term follow‐up of autoimmune thrombocytopenic purpura (ATP) patients submitted to splenectomy
Authors: Mazzucconi Maria Gabriella , Arista Maria Cristina , Peraino Monica , Chistolini Antonio , Felici Carla , Francavilla Vittorio , Macale Elvira , Conti Laura , Gandolfo Giuseppe Maria 
Published: July 2010

Abstract:  We studied the general outcome in 94 adult patients with autoimmune thrombocytopenic purpura (ATP) submitted to splenectomy. Of 84/94 patients who presented a complete or partial response 30 d after splenectomy, 16 (19%) showed one or more relapses. The clinical situation of the 81 patients still under observation is as follows: 13 unrensponsive, 60 completely or partially responsive, without relapses during the follow‐up, 8 completely or partially responsive after one or more relapses. No correlation was found between the favourable splenectomy outcome and age at splenectomy, the diagnosis‐splenectomy interval and initial response to corticosteroids. The probability of disease‐free survival is 83%, projected at 10 yr, while the overall survival is 93%, projected at 10 yr.PAIgG levels of the normal subjects and of responding patients were found to be similar, while in the groups of non‐responding/relapsing patients, significantly higher values of PAIgG were detected, as compared to the control group.
Somatic mutations and intraclonal variations in the rearranged Vk genes of B‐non‐Hodgkin's lymphoma cell lines
Authors: Gabay C. , Ben‐Bassat H. , Schlesinger M. , Laskov R. 
Published: July 2010

Abstract:  Three established Burkitt's lymphoma (BL) cell lines (Daudi, Raji and DG‐75) and three B‐non‐Hodgkin's lymphoma (B‐NHL) of other types (Pfeiffer, Farage and Toledo) were analyzed with respect to the presence of somatic point mutations in their rearranged immunoglobulin Vk genes. Two of the Vk sequences of BL and two of those of the B‐NHL were heavily mutated (up to 11%), when compared with their closest germline variable region counterparts (“clonal mutations”). Only one of the six cell lines contained an unmutated germline Vk sequence. The clonal mutations have features characteristic of the mutation machinery operating in the course of the T‐dependent immune response, such as a preference of mutations in purine bases, more transitions than transversions and targeting to CDR and to known “hotspot” motifs. Sequence variations among different Vk PCR clones isolated from each of the cell lines (“intraclonal mutations”) showed that the Vk of Toledo exhibited about 5‐fold higher mutation frequency (MF) than the background level of Taq polymerase error (˜0.12% mut/bp). Similarly, the MF of Vk of two of the BL cell lines was 3–4‐fold higher than the Taq polymerase misincorporation rate. In contrast, the mutation frequencies of the Vk of DG‐75, Farage and Pfeiffer did not significantly exceed the level of Taq polymerase error.Our combined results show that 5 out of the 6 B‐cell lines studied originated from B‐cells that have already somatically mutated in vivo their rearranged Vk genes. Moreover, two of the Burkitt's and one of the B‐NHL cell lines exhibit intraclonal variation indicating that the process of somatic hypermutation continued following the neoplastic event, either in vivo or in culture. These results are in accord with the presumed origin of the majority of the BL and some types of the B‐NHL, from centrocytes or centroblasts of the germinal centers in which the process of somatic hypermutation is taking place.
Increased vascularization in myeloma
Authors: Laroche M. , Brousset P. , Ludot I. , Mazières B. , Thiechart M. , Attal M. 
Published: July 2010

Abstract: Several studies have shown that the number of intratumoral vessels can predict the aggressiveness of a solid cancer, development of metastases and patient survival. Does angiogenesis play an important role in myeloma?The aim of our study was to quantify bone marrow vascularity in various stages of proliferative plasma cell disorders (monoclonal gammopathies of undetermined significance (MGUS), stage I multiple myeloma (MM), stage III MM and Waldenström's macroglobulinemia (WM)) and to compare it with that of patients with osteoporosis.The study included 15 MGUS patients, 15 patients with stage I MM, 15 patients with symptomatic stage III MM, 7 patients with WM, 10 patients with osteoporosis, and 10 patients with reactive bone marrow (RBM), matched for sex and age. After iliac crest biopsy, the various vessels (arterioles, capillaries and sinusoids) were labeled with monoclonal antibodies CD34 and counted, and a histomorphometric study was done. The number of arterioles and arterial capillaries was significantly increased in MGUS and myeloma compared with osteoporosis. The number of arterioles and arterial capillaries increased moderately according to the stage of gravity of myeloma. The number of arterioles is negatively correlated with the trabecular bone volume and positively correlated with the eroded surfaces.
The radiotherapy reference panel – experiences and results of the German Hodgkin Study Group (GHSG)
Authors: Eich Hans Theodor , Müller Rolf‐Peter 
Published: July 2010

Abstract:  Objective:  The German Hodgkin Study Group (GHSG) including more than 500 participating centers established a central radiotherapy (RT) reference center to improve quality of treatment. The purpose of the present article is to summarize the experiences and results of the performed and ongoing quality assurance programs (QAP) of RT.Methods:  A panel of expert radiation oncologists evaluated retrospectively the adequacy of treatment fields, applied radiation doses, treatment time and technical parameters. For the fourth study generation (HD10–12, 1998–2003), the RT reference center moved from Munich to Cologne. New RT QAP were initiated according to the demands of the new trials and former programs were enhanced.Results:  A strong achievement in the era of extended field RT was to show that major deviations of radiation treatment portals and radiation dose from prospective treatment prescriptions were unfavorable prognostic factors for patients with early‐stage Hodgkin's lymphoma (HL). The central prospective radiation oncological review of all diagnostic imaging showed that corrections of disease involvement in 49% of patients with early stages (HD10) and in 67% for patients with intermediate stages (HD11) were necessary. The introduction of electronic image transfer optimized and simplified the workflow of the QAP.Conclusion:  Today radiation oncologists in the GHSG perform efficient QAP to improve treatment quality of study patients. For early‐stage HL a central prospective review of all diagnostic imaging is performed to control the disease extension and to define the IF treatment volume. Retrospective analysis of RT portals detects faults in the applied irradiation.
CD34+ dose‐driven administration of granulocyte colony‐stimulating factor after high‐dose chemotherapy in lymphoma patients
Authors: Todisco Elisabetta , Castagna Luca , Sarina Barbara , Mazza Rita , Magagnoli Massimo , Balzarotti Monica , Nozza Andrea , Siracusano Licia , Timofeeva Inna , Anastasia Antonella , Demarco Monica , Santoro Armando 
Published: July 2010

AbstractOur goal was to optimize use of granulocyte colony‐stimulating factor (G‐CSF) after high‐dose chemotherapy and autologous peripheral blood stem‐cell transplantation in lymphoma patients, limiting G‐CSF administration to patients infusing a suboptimal CD34+ cell number. Of 124 consecutive patients with histologically proven Hodgkin's and non‐Hodgkin's lymphoma from January 2001 to June 2004, 60 patients (group 1) given ≥5 × 106/kg CD34+ cells received no G‐CSF; 64 patients (group 2) given ≤5 × 106/kg CD34+ cells received G‐CSF from day +5 after stem‐cell reinfusion. The median times to reach 0.5 × 109/L and 1.0 × 109/L neutrophils were, respectively, 3 and 4 d shorter in G‐CSF group and this difference was statistically significant (P = 0.0014; P = 0.0001). In terms of antibiotic and antimycotic requirements, gastrointestinal toxicity, days of hospitalization, and transfusion requirements, no differences were demonstrated between the two groups. No statistically significant difference was demonstrated for the total number of febrile episodes (52 for group 1; 53 for group 2; P = 0.623) and the median number of febrile days (2 d for both groups). Myeloid reconstitution values for both groups agree with published results for autotransplanted patients treated with G‐CSF from 7 to 14 d. Also, major clinical events, antibiotic, antimycotic, and transfusion requirements, and hospital stay were similar to published findings. Our data suggest that G‐CSF administration can be safely optimized, used only for patients infused with a suboptimal CD34+ cell dose.
Ifosfamide, etoposide, cytarabine, and dexamethasone as salvage treatment followed by high‐dose cyclophosphamide, melphalan, and etoposide with autologous peripheral blood stem cell transplantation for relapsed or refractory lymphomas
Authors: Schütt P. , Passon J. , Ebeling P. , Welt A. , Müller S. , Metz K. , Moritz T. , Seeber S. , Nowrousian M. R. 
Published: July 2010

AbstractHigh‐dose chemotherapy (HD‐CT) with autologous stem cell transplantation is considered to be the treatment of choice for relapsed high‐grade non‐Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL) patients, but the optimal treatment has not yet been defined. We evaluated a salvage treatment regimen consisting of conventional cycles with ifosfamide, etoposide, cytarabine, and dexamethasone (IVAD) followed by two cycles of HD‐CT consisting of cyclophosphamide, melphalan, and etoposide (CMV) with autologous stem cell support in patients with relapsed or refractory NHL (n = 59) and HL (n = 16). Response to IVAD was complete remission (CR) in 16 patients (21%), partial remission (PR) in 39 patients (52%), stable disease (SD) in 18 patients (24%), and progressive disease (PD) in two patients (2.7%). Of 70 patients treated with HD‐CT, 41 patients (59%) showed a CR, 20 patients a PR (29%), eight patients a SD (11%), and one patient a PD (1.4%). The 5‐yr overall survival for the entire group of patients was 29%, and for patients with NHL and HL 25%, and 38%, respectively. The respective event‐free survival probabilities at 5 yr were 22%, 16%, and 31%. Seven treatment‐related deaths due to septicemia (three), cardiac arrhythmia (one), pneumonia (one), pneumonitis (one), and toxic epidermal necrolysis (one) were observed. In multivariate analysis, an International Prognostic Index of ≥2 and resistant disease to first‐line chemotherapy were poor independent prognostic factors for the subgroup of patients with NHL. In conclusion, these results indicate that IVAD/CMV is feasible as a salvage therapy for lymphoma patients. This treatment is currently evaluated with the addition of rituximab.
Graft rejection and hyperacute graft‐versus‐host disease in stem cell transplantation from non‐inherited maternal antigen complementary HLA‐mismatched siblings
Authors: Okumura Hirokazu , Yamaguchi Masaki , Kotani Takeharu , Sugimori Naomi , Sugimori Chiharu , Ozaki Jun , Kondo Yukio , Yamazaki Hirohito , Chuhjo Tatsuya , Takami Akiyoshi , Ueda Mikio , Ohtake Shigeki , Nakao Shinji 
Published: July 2010

AbstractHuman leukocyte antigen (HLA)‐mismatched stem cell transplantation from non‐inherited maternal antigen (NIMA)‐complementary donors is known to produce stable engraftment without inducing severe graft‐versus‐host disease (GVHD). We treated two patients with acute myeloid leukemia (AML) and one patient with severe aplastic anemia (SAA) with HLA‐mismatched stem cell transplantation (SCT) from NIMA‐complementary donors (NIMA‐mismatched SCT). The presence of donor and recipient‐derived blood cells in the peripheral blood of recipient (donor microchimerism) and donor was documented respectively by amplifying NIMA‐derived DNA in two of the three patients. Graft rejection occurred in the SAA patient who was conditioned with a fludarabine‐based regimen. Grade III and grade IV acute GVHD developed in patients with AML on day 8 and day 11 respectively, and became a direct cause of death in one patient. The findings suggest that intensive conditioning and immunosuppression after stem cell transplantation are needed in NIMA‐mismatched SCT even if donor and recipient microchimerisms is detectable in the donor and recipient before SCT.
Do cytogenetic abnormalities precede morphologic abnormalities in a developing malignant condition?
Authors: Northup Jill K. , Gadre Swarupa A. , Ge Yimin , Lockhart Lillian H. , Velagaleti Gopalrao V. N. 
Published: July 2010

AbstractCytogenetic evaluation of bone marrow and neoplastic tissues plays a critical role in determining patient management and prognosis. Here, we highlight two cases in which the cytogenetic studies challenge the common practice of using hematologic and morphologic changes as key factors in malignant disease management. The first case is that of a lymph node sample from a 40‐yr‐old non‐Hodgkin's lymphoma (NHL) patient sent for determination of disease progress. Hematologic studies showed no evidence of transformation to high‐grade NHL (>15% blasts with rare mitotic figures). Cytogenetic studies of lymph node showed multiple clonal abnormalities, most notably a der(18) from a t(14;18) which is associated with high‐grade NHL. After two cycles of chemotherapy with fludarabine, the patient did not show any clinical response, suggesting possible progression to high‐grade lymphoma. The second case is of a patient with a history of human immunodeficiency virus and blastic natural killer leukemia/lymphoma. Hematologic studies of ascitic fluid classified the patient as having pleural effusion lymphoma whereas bone marrow analysis showed no malignancy. Bone marrow cytogenetic studies showed multiple clonal abnormalities including a t(8;14), which is commonly associated with Burkitt's lymphoma (BL). To our knowledge, this is the first case wherein a morphologically normal bone marrow showed presence of clonal abnormalities consistent with BL or Pleural effusion lymphoma. After two cycles of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy, the patient's general condition and ascitis improved and she was discharged. These studies clearly demonstrate that genetic changes often precede morphologic changes in a developing malignant condition. Therefore, the critical information needed for care of patients with malignant disorders may be incomplete or inaccurate if cytogenetic evaluation is overlooked.
Intravascular B‐cell lymphoma with leukemic presentation: case report and literature review
Authors: Xanthopoulos Vasilios , Galanopoulos Athanasios G. , Paterakis Georgios , Apessou Dimitra , Argyrakos Theodoros , Goumakou Eleni , Papadhimitriou Stephanos I. , Savvidou Ioanna , Georgiakaki Maria , Anagnostopoulos Nikolaos I. 
Published: July 2010

AbstractIntravascular lymphoma is an extremely rare, disseminated, and aggressive extranodal CD20+ non‐Hodgkin’s lymphoma characterized by the presence of lymphoma cells only in the lumina of small vessels. We report a 72‐year‐old woman with a diagnosis of intravascular lymphoma presented with splenomegaly and leukemic appearance in the peripheral blood smear. Her clinical course was rapidly deteriorated before the initiation of specific chemotherapy and finally died due to multiorgan insufficiency. Bone marrow biopsy revealed a characteristic infiltration of CD5, CD10 B‐cell lymphoma. To our knowledge, this is the first reported case of a CD5, CD10 intravascular B‐cell lymphoma with leukemic presentation in peripheral blood with multiple cytogenetic aberrations.