bluuebunny/crossref_metadata_2025_split huggingface dataset:
Allogeneic Stem Cell Transplantation for Relapsed Hodgkin’s Disease - a Single Centre Experience
Authors: Scheid Christof , Borchmann Peter , Bredenfeld Henning , Chemnitz Jens , Holtick Udo , Cremer Birgit , Bergwelt-Baildon Michael , Hallek Michael , Engert Andreas 
Published: April 2020

Abstract
Hodgkin’s disease can be cured by chemotherapy in the majority of cases. However a small proportion of patients show an aggressive course with multiple relapses after chemotherapy including autologous stem cell transplantation. Whether allogeneic stem cell transplantation constitutes a valid therapeutic option for these patients remains highly controversial. We report on our experience on 9 patients with Hodgkin’s disease receiving an allogeneic stem cell transplant from matched related (n=3), matched unrelated (n=1) or mismatched unrelated (2× 9/10, 2 ×8/10, 1× 7/10) donors. Median age was 28 years (range 18 – 35). All patients were extensively pre-treated including high-dose chemotherapy with autologous stem cell transplantation in 8 of 9 cases. The disease status before transplantation was CR (n=1), PR (n=5), SD (n=2) or progressive disease in 1 case. Conditioning treatment consisted of fludarabine 30 mg/m2 day -8 to -4, melphalan 70 mg/m2 day -3 to -2 and ATG 10–20 mg/kg day -4 to -2. Ciclosporin A and short course methotrexate was used for prophylactic immunosuppression. All patients showed prompt engraftment. Acute GvHD was found in 2 patients (Grade IV n=1, Grade I n=1), chronic GvHD did not occur after a median follow up of 471 days for the surviving patients. Two patients died from treatment-related causes, one from GvHD and one from septicemia. Estimated 2 year survival is 78%. Three patients have relapsed so far at day 128, 192 and 201 post transplant and received donor lymphocyte infusions or chemotherapy. The estimated 2 year disease free survival is 57%. Our results show a good feasibility of an allogeneic stem cell transplantation with reduced intensity conditioning for relapsed Hodgkin’s disease despite extensive pre-treatment and mostly partial remissions at transplant. The rate of acute and chronic GvHD was remarkably low in view of the fact, that 5 of 9 patients had mismatched unrelated donors. In summary allogeneic stem cell transplantation should be further exploited as treatment option for refractory and relapsed Hodgkin’s disease in younger patients.
Late Platelets Recovery after Autografting (ASCT) in Patients with Acute Myeloid Leukemia (AML) Is A Prognostically Favourable Factor for Long-Term Remission
Authors: Carella A. M. , Catania G , Varaldo R , Nati S , Congiu A , Vimercati R , Rossi E , Spriano M 
Published: April 2020

Abstract
Althought favourable results with ASCT in patients with AML in first CR have been reported, there are no definitive data indicating that this approach is superior to chemotherapy alone. We have recently reviewed our 23 years experience with ASCT in AML in Genoa. From January 1984 to December 2007, 79 patients in first CR, aged 18–65 years, who did not have a sibling donor, were autografted. These patients had been previously treated in induction with Ara-C 200 mg/m2/d × 7 days and DNR 50 mg/m2/d × 3 days. Soon after, they had received consolidation therapy with 4 courses of DAT therapy (DNR 50 mg/m2/d1, Ara-C 200 mg/m2 c.i. day 2–5, thioguanine 80 mg/m2 days 2–5). Fifty patients were autografted with bone marrow and 29 patients with peripheral blood stem cells. High-dose therapy consisted of Cyclophosphamide and single dose TBI (n=50) or high-dose busulfan and cyclophosphamide (n=29). At a median of 11 years, 15 patients (19%) are still alive and well. At that time genetic aberrations combined or not with cytogenetics were not available; therefore we have retrospectively analyzed the patients according to age, sex, WBC count, time to CR and conditioning regimen. None of these factors was predictive for long-term remission. On the contrary, we found that late platelets recovery was predictive. The median time to recover platelets &gt; 50 × 109/L was 72 days (45–115 days) in long-term remission patients versus ≤ 30 days in the other patients who relapsed. During the presentation details of this retrospective study will be discussed. In conclusion, the late recovery of platelets after autografting is in our experience the most predictive factor for long-term remission duration in autografted AML patients.
Single Autologous Stem Cell Transplant Using Busulfan and Cyclophosphamide as Conditioning Regimen in Patients with Multiple Myeloma
Authors: Talamo Giampaolo , Claxton David F. , Drabick Joseph , Dougherty David W. , Sivik Jeff , Ehmann Christopher W. , Rybka Witold 
Published: April 2020

Abstract
Autologous peripheral blood stem cell transplantation (ASCT) has been shown to improve survival in patients with multiple myeloma (MM). High-dose melphalan is considered the current standard of care among the preparative regimens used in ASCT for MM patients. We report the results of ASCT in 79 consecutive MM patients using a conditioning regimen with busulfan and cyclophosphamide (Bu/Cy), given as single ASCT and without maintenance therapy. Peripheral blood stem cells were mobilized with cyclophosphamide 5,000 mg/m2 IV + etoposide 1,000 mg/m2 IV, followed by granulocyte colony stimulating factor (G-CSF) 5 mg/Kg/day until the end of stem cell collection. A median of 41.1 × 106 CD34+ cells/Kg (range, 2.1–139.7 × 106) of ideal body weight were mobilized. The conditioning regimen consisted of busulfan 1 mg/Kg PO or 0.8 mg/Kg IV every 6 hours x 16 doses (days -7 to -3), and cyclophosphamide 60 mg/Kg/day IV for 2 days (days -3 to -2). Patients achieved neutrophil engraftment (absolute neutrophil count &gt;500/μL) at a median of +13 days (range, +6 to +21 days), and platelet engraftment (platelets &gt;20,000/μL unsupported by transfusion) at a median of 14 days (range, +11 to +24). Using a transfusion threshold of hemoglobin &lt;8.0 g/dL and platelets &lt;10,000/μL, patients required a median of 2 units of RBC transfusions (range, 0–8), and 1 platelet transfusion (range, 0–15) until hematologic engraftment. Forty-eight and 20 patients reached PR and CR, respectively, for an overall RR of 86%. At a median followup of 41 months (range 2–132 months), the estimated median overall survival (OS) and progression-free survival (PFS) were 45 months [95% confidence interval (CI) = 38–92] and 20 months (95% CI = 15–25), respectively. Veno-occlusive disease developed in 4 pts, and it was lethal in 1 of them. The Bu/Cy regimen was overall well tolerated, and transplant-related mortality was 4%. No statistically significant difference in terms of OS and EFS were observed between the group of patients receiving oral (n=13) vs IV busulfan (n=66). OS was not statistically different between the group receiving ASCT in first remission (n=62) and the group receiving ASCT as salvage therapy, i.e., upon MM progression (n=17), either calculating OS from the day of ASCT or from the day of MM diagnosis. We conclude that our reported clinical outcomes of the Bu/Cy regimen are equivalent to those obtained in historical controls with high-dose melphalan followed by a single ASCT. Thus, given the equivalent effectiveness but greater complexity of administration of the Bu/Cy regimen compared with that of single agent melphalan, we believe the latter should remain the agent of choice for ASCT in MM.
Autologous Hematopoietic Stem Cell Transplantationfor Adult with Acute Leukemia in First Complete Remission
Authors: Zhou Huifen , Depei Wu , Tang Xiaowen , Sun Aining , Jin Zhengming , Qiu Huiying , Miao Miao , Fu Chengcheng , He Guangsheng , Han Yue 
Published: April 2020

Abstract
Objective The objective of this study was to evaluate the clinical outcome of autologous hematopoietic stem cell transplantation (AHSCT) for acute leukemia(AL).
Methods The outcome of 56 AL patients who received autologous HSCT(AHSCT) for AL in first complete remission (CR) from May 2001 to May 2008 were analyzed retrospectively. There were 31 males and 25 females, the median age was 25(11~ 57)years. The diagnosis of these patients were acute myeloid leukemia (AML, n=38), acute lymphocytic leukemia(ALL, n=17) and acute hybrid leukemia (AHL, n=1). Patients were divided into low/moderate risk group (n=46) and high risk group (n=10) according to their characteristics of newly diagnosis. If the patient achieved first complete remission(CR), one to three courses of intensification chemotherapy containing high dose cytarabine(HDAC)were given. All the patients were in CR1 before AHSCT. Stem cells were mobilized with MAG regimen which composed of HDAC, Mitoxantrone and G-CSF. The conditioning regimen consisted of modified BU/ CY for AML patients or total body irradiation (TBI) plus cyclophosphamide (CTX) for ALL patients. Patients received consolidation chemotherapy every 3 months after AHSCT until 3 years post transplant. Nine patients received several course of cytokine-induced killer (CIK) cells treatment.
Result The median number of MNC and CD34 positive cell was 6.9(1.2 `21)×108/kg and 2.3(1.6 `6.3)×106/kg respectively. All patients achieved hemopoietc recovery. The median time of the engraftment of neutrophil and platelet was 9.7(8 `14) days and 12.9(9 `20) days posttransplant respectively. The incidence and severity of regimen-related toxicity were mild. The incidence of treatment related mortality (TRM)is 0%. The median follow-up of surviving patients was 31 months(range, 2 `86). Until now 46 patients are still alive, including 4 relapse cases. 13 cases were died of relapse. The five-year overall survival(OS) and the leukemia-free survival(LFS) were 77.3% and 71.9% respectively. The incidence of relapse was 23.2%. The OS and LFS in the low /moderate risk and high risk AL cohorts were 85.7%versus 40% and 79%versus 40% respectively(P&lt;0.01)
Conclusion AHSCT is the first option for the AL patients who were in good or moderate risk group and had achieved first complete remission. Regular consolidation chemotherapy after transplantation was beneficial to improve the LFS of AL patients.
Expression Profile of Selected HOX Genes in Different Childhood ALL Subtypes
Authors: Vicenova Blanka , Krejci Ondrej , Zaliova Marketa , Muzikova Katerina , Starkova Julia , Pospisek Martin , Drabkin Harry A. , Trka Jan 
Published: April 2020

Abstract
Homeobox-containing (HOX) genes represent a large family of transcription factors that are involved in anteroposterior pattern formation during embryonic organogenesis. Besides their role in ontogenesis, various HOX genes have been associated with haematologic disorders including leukaemia. Multiple studies revealed that dysregulation of HOX genes is relevant to AML, ALL and CML; in addition, HOX genes are rearranged in some cases of human leukaemia and make part of fusion proteins such as NUP98-HOXA9, PBX1-E2A, etc. We have previously studied the pattern of HOX gene expression in chromosomally defined subsets of acute myeloid leukaemia and have shown that HOX genes exhibit a specific expression pattern throughout the AML subsets that can be related to the patient outcome. In this study, we studied the expression profile of various HOX genes in childhood acute lymphoblastic leukaemia (ALL) subtypes. We analysed mRNA levels of 23 different homeobox-containing genes in 59 children patients with ALL that were divided into six groups based on cytogenetic abnormalities and prednisone responsiveness: BCR/ABL, hyperdiploid ALL, TEL/AML1, MLL/AF4, T-ALL, prednisone good responders (PGR) and prednisone poor responders (PPR). Patient cDNA samples were analyzed using SYBRGreen I real-time quantitative PCR (qRT-PCR) and data obtained were normalized to the expression of ABL control gene. Our data indicate that certain HOX genes including HOXA3, HOXA4, HOXA5, HOXA6, HOXA9, HOXA10, HOXB2 or HOXB3 are differentially expressed throughout the ALL subtypes. Most notably, HOXA4, HOXA9, HOXB2 and HOXB3 mRNA levels appear to be elevated in T-ALL patients; hyperdiploid ALL patients display increased HOXA5 mRNA levels and HOXA3, HOXA6, HOXA9 and HOXA10 expression is higher in patients bearing the MLL/AF4 fusion gene. A relatively high level of HOXA5, HOXB2 and HOXB3 expression was observed in all patient groups. Furthermore, HOX gene expression distinguishes PGR from PPR group of patients; this divergence is most apparent in the case of HOXB2, HOXB3 and HOXB7. This study shows potential prognostic relevance of HOX gene levels in patients with childhood ALL. Data also confirm the differential HOX gene expression in various childhood ALL subtypes and underline the importance of certain HOX genes in leukemogenesis.
Molecular Variability of FLT3/ITD Mutants and Their Impact on the Differentiation Program of 32D Cells: Implications for the Biological Properties of AML Blasts
Authors: Pekova Sona , Dvorak Michal , Ivanek Robert , Rueggeberg Sabrina , Leicht Stefan , Kozak Tomas , Vrba Jiri , Schwarz Jiri , Cetkovsky Petr , Prucha Miroslav , Hrusak Ondrej 
Published: April 2020

Abstract
FLT3 is the most frequently mutated gene in AML – up to 40% of AML harbor an activating mutation within FLT3 gene. Though AML is a relatively rare disease, such a high mutability rate, as observed with FLT3 gene, is striking. To elucidate the molecular background of this phenomenon, we have established nine unique FLT3/ITD - carrying 32D cell lines and a set of controls, and subjected them to whole genome expression analysis and 2DE LC/MS proteomics. Data obtained on this so far largest set of ITD mutants indicates that FLT3/ITD positive cells exhibit less mature expression profiles resembling ST-HSC and MkEP/CMP/LMPP progenitors. FLT3/ITD-positive 32D cells overexpress a combination of genes of pluripotency (Etv5, endoglin, EpoR, Mpl, Trfr2, GATA.2, Hemgn, Myb, Dok2, Gli1, Pim3, PML, Ikaros, Pum1, Dlx4, Hox-c8, HoxB9, Runx1, c-Myc, Shh, FL) and early erythroid precursors (EpoR, Trfr2, GATA.1, Klf1), implicating their less mature expression profile than 32D cell lines harboring wild type FLT3 or 32D controls. We hypothesize that FLT3/ITD might contribute not only to the proliferative advantage of FLT3/ITD positive cells, but also to their reprogramming towards less differentiated stages, thus strengthening their malignant properties. This finding might explain the pronounced mutation rate of the aberrantly expressed FLT3 gene in AML, and, also, the inferior prognosis of FLT3/ITD positive AML patients. Moreover, the microarray data has revealed biological differences among individual ITD variants – a finding supporting the recent clinical data on the prognostic impact of the size of individual ITDs.
Factor V Deficiency in a Patient with Polycythemia Vera and Huntington’s Chorea
Authors: Girtovitis Fotios I , Diamantidis Michael D. , Kaiafa Georgia , Constantinou Nikolaos , Lazaridou Despina , Saouli Zoi , Ntaios George , Kontoninas Zisis , Andreadis Charalambos , Papadopoulos Athanasios 
Published: April 2020

Abstract
Factor V deficiency is a very rare congenital disorder of blood coagulation, which was initially described by Owren in 1947. Ever since it is estimated that approximately 150 cases have been reported worldwide. We describe a case of a 31-year-old female, who was referred to the hemostasis unit of our clinic for investigation of a prolonged prothrombin time (PT) [PT: 14.8″ (control 12″)], along with a prolonged activated partial thromboplastin time (aPTT) [aPTT: 41.9″ (control 31.5″)]. These disorders were discovered in a pre-operating check-up, before being subjected to a removal of a thyroid gland node. Her medical history revealed that she had been diagnosed with polycythemia vera 6 years before, as well as Huntington’s chorea almost a decade earlier. The patient was under phlebotomy therapy once or twice a month, with no other specific treatment. She received acetylsalicylic acid (100mg/day), because of polycythemia vera, which had to be discontinued, due to mild ecchymoses and menometrorrhagia. Apart from the bleeding tendency mentioned above (attributed to administration of acetylsalicylic acid), no other hemorrhagic manifestations arose from her whole medical history. Her hematological profile was as follows: WBC: 7500/μl, Hb: 14,4 g/l, PLT: 710.000/μl. The patient’s hepatic and renal examination was normal. Repeat PT and aPTT after mixing with normal plasma gave normal results, thereby excluding the presence of a coagulation inhibitor and indicating deficiency of a factor in the common pathway. Factor V assay was done and it was found to be 15%. The examination of the rest coagulation factors was within normal range. The possible association of such a coagulation disorder with the aforementioned diseases has not been established until today. We therefore consider interesting the case described, not only because of its rarity, but also because of its underlying pathology and concomitant disease.
Thromboelastogram Platelet Mapping Accurately Predicts Bleeding Phenotype in Glanzmann Thrombasthenia
Authors: Callaghan Michael U , Chitlur Meera B. , Lusher Jeanne M. , Rajpurkar Madhvi , Fleming Patricia 
Published: April 2020

Abstract
Glanzmann thrombasthenia (GT) is caused by genetic defects in the ITGA2B and ITGB3 genes that encode the proteins of the αIIbβ3 complex on the surface of the platelet. The αIIbβ3 complex on activated platelets acts a receptor principally for fibrinogen but can also bind fibronectin, vonWillebrand factor, vitronectin and CD40 ligand under conditions of high flow. The binding of these proteins results in the formation of protein bridges and aggregation of platelets. Patients with GT have deficiency of platelet surface αIIbβ3 resulting in insufficient platelet spreading and aggregation and resultant bleeding. Conventional platelet aggregation studies demonstrate aggregation with ristocetin but absence of aggregation with other platelet agonists including thrombin, collagen, arachadonic acid and epinephrine. Platelet immunophenotyping demonstrates absent (Type I) or diminished (Type II) surface expression of CD41 (Gp IIb) and CD61 (Gp IIIa). Bleeding phenotype in individual patients can be quite variable and is not well predicted by surface expression or platelet aggregation studies.
Thromboelastogram platelet mapping (TEG-PM) is a newer technology that employs antagonists of coagulation cascade meditated thrombosis in concert with platelet agonists to determine the level of platelet inhibition. Here we have examined the bleeding phenotype (Table I) of 5 GT patients, from three separate families, followed at our center in relation to conventional platelet aggregation studies, platelet immunophenotype and TEG-PM (Figure I). Three of the patients are from a single kindred and have had frequent severe bleeding episodes requiring treatment with activated FVII, transfused platelets and transfusion support for blood loss. The fourth patient has had an intermediate bleeding phenotype. The fifth patient has had only a single severe bleeding episode after nasal surgery and an otherwise mild bleeding phenotype including a caesarian section with a single platelet transfusion and no bleeding. The fifth patient displayed reduced CD41 and CD61 platelet expression (type II GT) while the other 4 patients have no CD41 and CD61 platelet expression (type I GT) by flow cytometry. While all 5 patients have similar, classic platelet aggregation studies the TEG-PM accurately predicted the bleeding phenotype. We believe TEG-PM may be a useful tool for the management of patients with GT.
Table I
Patient I Patient II Patient III Patient IV Patient V Age 4 years 10 years 20 years 2 years 29 years Sex Female Female Male Female Female # of PRBC Transfusion 0 2 0 3 0 Hospitilizations 2 4 7 4 1 FVIIa days 69 47 27 17 0 Platelet transfusions 9 3 13 0 1 PFA Epi &gt;262 s - - &gt;196 s 259 s PFA ADP 272 s - - &gt;210 s 173 s TEG K - - - 7.8 min 2.2 min TEG MA 13.6 13.4 16.4 22.8 65.9 Platelet Count 83–439K 91–364K 76–449K TEG ADP Inh 89.3% 100% 83.2% 100% 6.8% TEG AA Inh 98.7% 93.2% 89.7% 100% 68.6%
Figure I Figure I.
Spontaneous Resolution of Extreme Essential Thrombocytosis in a Child
Authors: Aviner Shraga , Schlesinger Menachem , Lugassy Gilles 
Published: April 2020

Abstract
Essential Thrombocytosis (ET) is rare in children and its clinical course is considered to be different from the adult disease. Unlike adults, most children with ET do not need treatment; however, children with extreme thrombocytosis present the treating physician with a therapeutic dilemma. We report a girl with a spontaneous resolution of extreme essential thrombocytosis. A 13 year old previously healthy girl presented to our ER with a 3 months history of intermittent mild abdominal pain with short episodes of diarrhea, intermittent episodes of paraesthesia in lower limbs and 3000 × 109/L platelets on CBC with pseudohyperkalemia of 6.4 mEq/L. Physical examination was unremarkable except for some diffuse mild tenderness on abdominal palpation. Laboratory work-up revealed normal WBC and Hb, Platelets 4100 × 109/L, mild microcytosis, Iron - 21.9 mcg/dL, transferin saturation 5.6%, serum potassium − 6.5 mEq/L, LDH 1000 IU. Liver, renal and thyroid function tests were within normal limits. PTT was mildly elevated 49.3 seconds (normal – 24.3–35), LAC-R mildly positive – 1.205 (0.8–1.20), KCT 58.2 sec. Anticardiolipin IgG −4.82 U/ml (negative), IgM - 11.24 U/ml (negative &lt; 7 U/ml). Anti dsDNA and Anti nuclear antibodies were negative. Studies for hypercoagulable state included Protein C, Antitrombin, Factor VIII, IX, XI, Factor V R506Q, and Apolipoprotein a; all were normal. A heterozygosity for PT G20210A was found, as well as homozygosity for MTHFR C667T with a normal level of Homocysteine (7.7mmole/L). Bone marrow aspiration showed increased cellularity of all cell lines, with many young megakaryocytes including some in clusters. No malignant cells were seen. Reticulin score on bone marrow biopsy was 0. Platelets function tests with adenosine di-phosphate and epinephrine were normal. Serum TPO level was 31.0 pg/ml (normal). A karyotype examination revealed a normal 46XX female. FISH for BCR/ABL was negative. DNA mutations for JAK2 on both the 12 and the14 exons and c-mpl mutations were not found. Spontaneous clone formation was normal. Helicobacter pylori IgG was 2.89 U/ml (normal) and stool was negative for parasites. Imaging studies included high resolution abdominal contrast CT scan, upper gastrointestinal tract imaging with gastrografin, Doppler sonography of splanchnic vessels and capsule endoscopy; all were interpreted as normal. Aspirin 75 mg/d was started without antimetabolite therapy. Abdominal pain and diarrhea gradually improved. After 3 month of antiagregant therapy, platelets count declined, gradually but steadily. One year after presentation the child is asymptomatic with platelet count of 600 × 109/L. The spontaneous remission of the extreme ET achieved by conservative treatment with no complications adds to the growing evidence, that childhood ET is a unique entity with different biology than adult ET, which might not need antimetabolite therapy.