bluuebunny/crossref_metadata_2025_split huggingface dataset:
Full Donor Chimerism in Both Plasma and Mononuclear Cell after Haematopoietic Stem Cell Transplant (HSCT) at D28 Is Predictive of Acute Graft-Versus-Host Disease but Not Disease Relapse or Graft Failure.
Authors: Ma Shing Yan , Au Wing Yan , Lei Albert K.W. , Tse Eric , Chim Chor Sang , Liang Raymond , Kwong Yok Lam 
Published: April 2020

Abstract
Mononuclear cell mixed donor/recipient chimerism has been shown extensively to have high predictive value in disease relapse and graft rejection. Recently, donor DNA in plasma of transplant recipient has been suggested as a potential tool for post HSCT monitoring for disease relapse and graft rejection but its role has not been defined. Moreover, the impact of GVHD on plasma donor DNA remains unknown. In the current study, both the plasma and mononuclear cell donor chimerism of 40 patients post HSCT (mean age = 40; 35 myeloablative, 5 non-myeloablative) were analyzed at D28. Each patient was followed-up for one year or when disease relapse/graft rejection occurred. GVHD of grade II or above was also recorded to establish its correlation with the chimerism status. At D28, all patients were engrafted and alive. 5 (13%) patients had full donor chimerism in both plasma and mononuclear cell (Group A), 7 (18%) patients had full donor chimerism in the mononuclear cell only but not the plasma (Group B) and 28 (70%) patients failed to have full chimerism in both plasma and mononuclear cell (Group C). The sex, age, HLA-matching, donor relationship and ABO blood group matching had no impact on the chimerism status. None of the Group A patient had disease relapse/graft rejection at 1 year when compared to 13/35 (37%) of Group B and C patients (p=0.154, not significant).However, all the patients in Group A had acute GVHD which was significantly more than those in Group B and C (5/5 vs 12/35, p=0.009) and the acute GVHD would not alter the chimerism status. These results provide a foundation for further research on the potential role of plasma donor chimerism in predicting disease relapse/graft rejection and GVHD so that early intervention can be instituted.
Increased Risk for EBV-Lymphoma after Allogeneic Hsct in Adult Lymphoma Patients?A Retrospective Study of Reduced Compared to Myeloablative Conditioning.
Authors: Hagglund Hans G. , Brune Mats , Oberg Gunnar , Hagberg Hans , Theorin Niklas , Remberger Mats , Kimby Eva 
Published: April 2020

Abstract
The aim of this study was to compare the outcome of allogeneic HSCT after myeloablative versus reduced intensity conditioning (RIC) for lymphoma.
From January 1984 to June 2004, 87 patients underwent HSCT for lymphoma (including 41 patients with RIC, all grafted after May 1998). The diagnoses were 15 and 24 aggressive, 18 and 17 indolent and 8 and 5 HD lymphomas, in the RIC and myeloablative groups, respectively. There were 64 males and 23 females. The median age was 40 (16–61). The donors were 3 identical twins, 55 related and 29 unrelated donors. The conditioning was based on chemotherapy only in 32 and 8 and irradiation in combination with chemotherapy in 9 and 38 patients (p&lt;0.001), in the RIC and myeloablative groups, respectively. Immunosuppression consisted of MTX and CsA in 68, CsA and MMF in 10, MTX or CsA in 4, T-cell depletion in 2 and 3 patients had no prophylaxis. In the RIC group the median age was significantly higher 49 (25–61) years than in the myeloablative group 38 (16–53) years (p&lt;0.001). PBSC was used in 36 (88%) patients in the RIC group versus 17 (37%) (p&lt;.001) in the myeloablative group.
The causes of deaths were 11 infections, 10 relapses, 6 EBV-lymphomas, 6 related to toxicity and 3 to GVHD and 1 renal cancer. Conclusions: Long term survival was seen in more than 50 % of patients with relapsing lymphoma after allogeneic HSCT. EBV lymphoma was the cause of death in 7% of the patients. The patient survival, TRM and relapse outcomes were similar after RIC and myeloablative conditioning but each subgroup is small. In the RIC group the patients were older, grafted in more advanced disease and the follow up shorter compared to the myeloablative group, therefore the results must be interpreted with care.
Results
RIC Myeloablative p GVHD (absolute incidence) Acute II-IV 43% 16% ns Chronic 32% 57% 0.06 Outcome (2-years probability) TRM 25% 39% ns Relapse 21% 16% ns Patient survival 61% 54% ns
Reduced Intensity Umbilical Cord Blood Transplantation(RI-UCBT) in Adult Patients with Graft Failure or Relapse after First Allogeneic Transplantation.
Authors: Masuoka Kazuhiro , Yuji Koichiro , Miura Yuji , Myojo Tomohiro , Kato Daisuke , Narimatsu Hiroto , Kusumi Eiji , Matsumura Tomoko , Wake Atsushi , Miyamoto Ko , Miyakoshi Shigesaburo , Yoneyama Akiko , Matsuzaki Michio , Ueyama Junichi , Morinaga Shinichi , Taniguchi Shuichi 
Published: April 2020

Abstract
Background: Graft failure, graft rejection, or disease relapse post allogeneic hematopoietic stem cell transplantation(HSCT) is life-threatening and serious complication that necessitate consideration for a second transplantation. Graft failure has been more frequently reported in patients with aplastic anemia with T-cell depletion of the graft, in cord blood transplants, or when unrelated or HLA-mismatched related donors were used. In second allogeneic stem cell transplant setting, current questions include suitable stem cell source, additional conditioning, immunosuppression, and the use of a different donor, still remain unknown. We performed a feasibility study of reduced intensity umbilical cord blood transplantation (RI-UCBT) in adult patients with graft failure or disease relapse after first allogeneic transplantation.
Patients and Methods: Nine patients (median age, 53 years; range 17–68) with advanced hematological diseases [AML (n=4), ALL (n=2), MDS (n=2), ATL (n=1)] who showed relapse or graft failure after first allogeneic transplantation underwent RI-UCBT with single cord blood unit at Toranomon Hospital between May 2003 and February 2004. Eight cases were in non-CR at transplant. A median time from first to second transplant was 226 days (range 31–475). The median number of mononuclear cells transfused was 2.3 x 107 /kg (range 1.8–3.5). HLA disparities were as follows; 5/6 in two cases, 4/6 in seven cases. Conditioning regimen mainly consisted of fludarabine 25 mg/m2 on days -7 to −3, melphalan 40mg/m2 (n=8) or busulfan 4mg/kg(n=1) day −3 to −2, and 4 Gy total body irradiation on day −1. Graft-versus-host disease (GVHD) prophylaxis was composed of ciclosporin alone (n=6) and tacrolimus alone (n=3).
Results: All of them achieved primary neutrophil engraftment (&gt;500/μL) after a median of 22 days (range, 15–32) and achievement of donor T-cell chimerism was confirmed. Four cases developed grade II-IV GVHD, and one case developed limited chronic GVHD. Of all the nine cases received RI-UCBT, seven died from relapse (n=4), sepsis (n=2), and TMA (n=1). Two survived without relapse for +232 and +81 days, respectively.
Discussion: Although the number of patients is small and the follow-up period is short, our results corroborate that RI-UCBT for graft failure or relapse post first transplant is tolerated and may be worth considering for further evaluation. Neutrophil engraftment was achieved, however, disease relapse rate and treatment-related mortality is high. The management of disease status and development of ideal conditioning regimen will be the focus of future investigation.
Allogeneic and Syngeneic Hematopoietic Cell Transplants in Patients with AL-Amyloidosis: A Report from the European Group for Blood and Marrow Transplantation (EBMT).
Authors: Schoenland Stefan O. , Baccarani Michel , Campbell Andrew , Carreras Enric , Cordonnier Catherine , Grommisch Leanthe , Leblond Veronique , Littlewood Timothy J. , Verdonck Leo F. , Wood L. , Zachee Pierre , Zander Axel R. , Goldschmidt Hartmut , Niederwieser Dietger , Gahrton Goesta 
Published: April 2020

Abstract
AL amyloidosis is caused by a plasma cell dyscrasia in which clonal immunoglobulin light chains deposited in tissues leads to organ failure and death. Treatment with high dose melphalan and autologous PBSC rescue produces hematologic remissions in approximately 40% of evaluable patients and improvements in organ disease and quality of life. For a subgroup of patients, an allogeneic hematopoietic cell transplantation (HCT) may be useful. There is little experience with this procedure in patients with AL amyloidosis. We report the patients (pts) who were registered within the EBMT database. Eleven pts (median age 45 years, range 30–63; 3 female) with AL amyloidosis (n=10) or with multiple myeloma plus AL amyloidosis (n=1) underwent allogeneic (n=8) or syngeneic ( n=3) HCT during 1987–2002, 7 of them before 2000. Donors of allogeneic transplants were matched related siblings. Main organ manifestations were kidney, heart and liver. Indications for allogeneic HCT were young age, relapse after autologous HCT (n=2) and progressive or refractory disease. Conditioning regimen was ablative in 4 pts and reduced-intensity conditioning (RIC) was used in the other 4 pts. Three pts had T cell depletion as graft-versus-host-disease (GvHD) prophylaxis. Engraftment was evaluable in 7/8 pts, 2 pts rejected their grafts and 5 pts had durable engraftment. One out of 5 evaluable pts developed acute GvHD (grade IV), and 1 of 3 evaluable pts developed chronic GvHD (limited disease). Five pts (62,5%) died at a median of 51 (range 25 – 83) days after HCT, all before day +100. From 4 of these 5 pts causes of death are known: 1 pt died of a cerebral aspergillosis (day +54) and 3 pts died of amyloidosis. Three pts remain alive (median observation 27 months, range 12–79) after HCT. Best hematological responses after HCT in surviving pts were immunofixation-negative CR in 1 pt (with cGvHD), PR in 1 pt and SD in the third pt. One of the 3 pts with syngeneic HCT is alive about 60 months after the procedure, the other 2 pts. died of TRM day +7 and +18, respectively. In summary, a very high day +100 mortality was observed. Main problem was cardiac failure due to amyloidosis in the very early phase after HCT. Half of the pts survived RIC and ablative conditioning, respectively. We conclude that a very restrictive patient selection is necessary to decrease mortality as it has been shown for high-dose chemotherapy with autologous HCT. Whether RIC plays an more important role for this patient group in the future remains to be defined.
Hematopoietic Recovery after Allogeneic Transplantation Using G-CSF-Mobilized and Cryopreserved Peripheral Blood Stem Cells (PBSC).
Authors: Akahane Daigo , Onishi Yasushi , Won Sung , Kami Masahiro , Mori Shin-ichiro , Heike Yuji , Takaue Yoichi , Tanosaki Ryuji 
Published: April 2020

Abstract
Although PBSC is being used more often, the long-term reconstitution kinetics of donor-derived hematopoiesis have not yet been fully determined particularly in PBSC transplantation with a reduced-intensity regimen (RIST). This study focused on the long-term follow-up of hematopoiesis in recipients who underwent allogeneic transplantation with G-CSF-mobilized and cryopreserved PBSC from an HLA-matched related donor from June 1999 to January 2004. A total of 144 patients were analyzed ; 55 received conventional stem cell transplantation (CST) with a myeloablative regimen, whereas 89 received RIST. After PBSC were mobilized by 3 to 5 days of subcutaneous injection of G-CSF at a dose of 10μg/kg/day, leukapheresis was performed using a Spectra (Gambro) or AS104 (Fresenius) cell separator. Apheresed products were centrifuged (270 x g, 20 min) and depleted of platelets. Cells were then cryopreserved with 10% DMSO, 20% autologous plasma and RPMI 1640 using a programmed freezer, and stored in LiqN2 until use. All patients received G-CSF 5μg/kg/day starting from day 6 after transplantation. Hematological data were examined during recovery, at day 100, 1 year and 2 years. The median number of infused CD34+ cells was 3. 9 x 106/kg (range, 1.8–7.8) in CST and 3.5 x 106/kg (1.4–7.8) in RIST. The median number of days to ANC &gt; 0.5 x 109/l and PLT &gt; 50 x 109/l were, respectively, 13 (9–25) and 14 (7–83) in CST, and 11 (1–15) and 12 (1–44) in RIST. There was no engraftment failure, and no significant relationship was observed between the CD34+ cell dose (at least in the range of 2.0 x 106/kg) and the speed of engraftment in either group. Grade II to IV acute graft-versus-host disease (GVHD) and extensive chronic GVHD occurred in 23/55 cases (42%) and 12/43 (28%) in CST, and in 37/89 (42%) and 19/60 (32%) in RIST, respectively. Each blood component in peripheral blood in non-relapsed patients remained essentially within the normal range (WBC &gt;3x109/l, Hb &gt;10g/dl, PLT &gt;1x1011/l) in 21/43 cases (49%) at day 100, in 25/26 (96%) at 1 year, and in 14/14 (100%) at 2 years in the CST group, whereas in the RIST group these values were 24/60 (40%) at day 100, 29/38 (76%) at 1 year, and 15/16 (94%) at 2 years, probably due to increased non-relapse complications including GVHD, etc. These results suggest that a CD34+ cell dose in PBSC of 2.0 x 106/kg before cryopreservation appears to be a good indication for stable long-term hematological recovery for both CST and RIST.
Factors Associated with Clinical Outcomes of 483 Allogeneic Peripheral Blood Stem Cell Transplants (PBSCT) in Brazil.
Authors: Vigorito Afonso C. , Aranha Francisco J.P. , Oliveira Gislaine B. , Eid Kátia A.B. , Lodi Fernanda M. , Azevedo Wellington M. , Colturato Vergílio , De Souza Mair P. , Barros José C. , Bittencourt Henrique , Silla Lúcia M.R. , Brandalise Silvia R. , Pontes Érica R. , Maiolino Angelo , Nucci Márcio , Ruiz Milton A. , Zanichelli Maria A. , De Souza Cármino A. 
Published: April 2020

Abstract
Uncertainty still exists with the effects of allogeneic PBSCT on the clinical outcomes of patients with hematological malignancies. Our aim was analyzed retrospectively the clinical outcomes of 483 patients who underwent an allo PBSCT in 9 Brazilians centers from May 1994 to February 2004. The analyzes included patients with hematological malignancies who underwent PBSCT from HLA identical siblings donors treated with G-CSF at a dose of 10mgr/kg/day, 5 days. Median age was 34ys old (2–57), advanced disease was present in 58%, conditioning without irradiation was 85%; GVHD prophylaxis with MTX/CsA was 91%; CD34+ median was 4.7X106/kg (0.51–71.6); the median follow-up for surviving patients was 797 days (8–3420); median day for neutrophils and platelets engraftment was 15 and 14, respectively; cumulative incidence (CI) for ³ 2 aGVHD was 38%; extensive cGVHD 63%; CI for transplant relate mortality (TRM) 59%; CI for relapse 37%; the estimates of OS and DFS at 9 ys are 33% and 42, respectively. The following factors were significantly associated with better outcomes for engraftment, aGVHD, cGVHD, OS, DFS, relapse, and TRM in univariate analyzes, respectively: neutrophils and platelets engraftment: CD34+ cell dose &gt; 2.8X106/kg, GVHD prophylaxis other than MTX/CsA, and sex match other than female donor for male recipient; aGVHD: age&lt;43ys old, and CD34 dose &gt; 4.7X106/kg; cGVHD: age &lt; 25ys, sex match other than female donor for male recipient, advanced disease and CD3+ dose &lt; 170X106/kg; OS: early disease; DFS: early disease, CD34+ dose &gt; 4.7X106/kg; relapse: age&gt; 25ys, CD34+ cell dose &gt; 2.8X106/kg, and early disease; TRM: early disease. All the results remained significant in multivariate analyzes, but CD34+ dose and platelet engraftment; age and CD34+ dose in aGVHD; age and CD3+ in cGVHD, and age in relapse. In our experience, sex match, CD34+ dose, GVHD prophylaxis may influence the engrafment, and sex match and disease phase the cGVHD. Furthermore, advanced disease had a negative impact on OS and TRM;. CD34+ higher dose and early disease were associated with better DFS and lower relapse.
B-Cell Depletion and Prevention of Hemolysis in Allogeneic Peripheral Blood Stem Cell Transplantation with Minor ABO Incompatibility.
Authors: Tavernier Emmanuelle , Thiebaut Anne , Nicolini Franck , Le Quoc Hung , Thomas Xavier , Chelghoum Youcef , Revesz Daniela , Hecquet Olivier , Dubost Philippe , Bourgeot Jean-Paul , Michallet Mauricette 
Published: April 2020

Abstract
Immune hemolysis is a severe complication of allogeneic peripheral blood stem cell (PBSC) transplantation with minor ABO-incompatibility, principally observed after conventional allogeneic PBSCT. The B-cell depletion of the PBSC graft is a prophylactic intervention which may decrease incidence and severity of this event. Eight patients who underwent allogeneic PBSCT in our institution between August 1999 and April 2004 were analysed. They all received a B-cell depleted transplantation performed because of minor ABO-incompatibility. There were 5 males and 3 females and the median age was 42.5 years (19–65). The pre-transplant diagnosis were solid tumours for 2 patients and haematological malignancies for 6. All received allogeneic PBSC recruited by G-CSF from 3 HLA identical unrelated and 5 HLA identical sibling donors. The median number of nucleated cells and CD34+ cells harvested were 7.75x108 /Kg (3.9–11) and 6x106/kg (4.3–8.7) and the median number of infused cells were 5.5x108 /Kg (3.4–8.71) and 5x 106/kg (3.1–8.33) respectively. Two patients received myeloablative and 6 patients reduced intensity conditioning regimens (RIC). As graft-versus-host-disease (GVHD) prophylaxis, cyclosporin with methotrexate was given after myeloablative conditioning. After RIC, cyclosporin alone (n=4) or cyclosporin associated to methotrexate (n=1) or cyclosporin associated to mycophenolate mofetil (n=1) were given. The ex-vivo manipulation consisted of a negative CD19 immuno-selection using the Isolex 300 I Baxter procedure. The median number of CD19+ cells (x106/kg) before and after ex-vivo manipulation was respectively 73 and 0.05, which represented a B-cell log depletion of 3.16. The ex-vivo manipulation nevertheless induced a nucleated cell depletion of 20% (from 7.75 x108 cells/kg to 5.52x108 cells/kg after B-cell depletion) and a CD34+ cell loss of 18.5% (from 6x106 cells/kg to 5x106 cells/kg). Engrafment was observed for all patients and median time to neutrophiles (&gt;0.5 G/l) and platelets (&gt;50 G/l) recovery were respectively 19 and 12 days. Acute GVHD occurred for 5 patients whereas 3 patients developed chronic GVHD. At last follow-up, 4 patients died, 3 due to progressive disease, one due to hepatic GVHD. None of these 8 patients developed any clinical severe hemolysis, except one patient who presented a biological hemolysis with the development of a positive antiglobulin test 3 weeks after transplantation, without any consequences. Three months after transplant and at the last follow-up, the 4 long-term alive patients showed a stable erythropoietic reconstitution with an ABO-RhD donor determination. These data indicate that B-cell depletion is an efficient and safe method which could be used in case of minor ABO incompatibility.
Reduced-Intensity Conditioning Regimen without Total Body Irradiation undergoing Umbilical Cord Blood Transplantation (non-TBI-RI-UCBT) Induces Successful Engraftment in Adult Patients with Advanced Hematological Malignancies.
Authors: Miyamoto Ko , Miyakoshi Shigesaburo , Kyo Aki , Yuji Koichiro , Kusumi Eiji , Sano Fumiaki , Taniguchi Shuichi , Nagosi Haruhisa 
Published: April 2020

Abstract
Purpose: In a phase I study to evaluate the feasibility and safety of non-TBI-RI-UCBT in patients with advanced hematological malignancies, who were ineligible for conventional allogeneic hematopoietic stem cell transplantation.
Patients and Methods: We treated a total of 6 patients (2 Hodgkin disease, 3 Follicular Lymphoma, 1 MDS overt leukemia). There were 4 female and 2 male, with a median age of 52.5 (46–62) years old. At the transplantation, all patients were in progressive disease (high-risk). Two patients with lymphoma had failed one or more preceding autologous transplants and a patient with overt leukemia had failed an allogeneic transplant. Backbone agent in the conditioning regimen was fludarabine, in combination with melphalan (n=4), or melphalan and thiotepa (n=2). Graft-versus-host disease (GVHD) prophylaxis incorporated cyclosporine alone (n=3), or FK506 alone (n=3). All of the patients received 4 of 6 HLA -antigen-matched umbilical cord blood transplantation. The median number of infused total nucleated cell dose and CD34 plus cell dose before freezing were 3.18 x 107 (2.77–4.7) /kg and 0,85 x 105 (0.57–1.91) /kg, respectively.
Results: All of the patients achieved primary neutrophil engraftment. The median time to reach 0.5 x 109/L neutrophils was 24 (13–31) days. Platelet counts above 20 x 109/L were achieved by 3 patients on median day of 40 (39–45) days. The median time to complete donor chimerism was 26.5 (16–35) days. Acute GVHD occurred in 2 of the 6 patients (grade I/II in 2). Chronic GVHD developed in none of the evaluable patients. Two of the 6 patients developed noninfectious fever before neutrophil engraftment. Three patients died of TRM (1 pneumonia, 1 thrombotic microangiopathy, 1 acute heart failure), and the other 2 patients died due to disease progression. At a median follow-up of 65.5 days (33–78), one of the 6 patients is currently alive in CR.
Conclusion: Although this study is preliminary with a small number of patients and short follow-up, our findings demonstrated the successful engraftment of non-TBI-RI-UCBT for adult patients with relapsed/refractory hematological malignancies. Prospective study to further evaluate the efficacy of non-TBI-RI-UCBT for hematological malignancies is warranted.
ENU Mutagenesis Screen Identifies a Novel Regulator of Platelet Production.
Authors: Stevenson William S. , Metcalf Donald , Hilton Douglas J. , Roberts Andrew W. , Alexander Warren S. 
Published: April 2020

Abstract
The genes that regulate variation in steady-state platelet count are largely unknown. We have attempted to identify novel genes that regulate platelet production by creating heritable models of thrombocytosis in mice by randomly inducing point mutations in the genome with chemical mutagenesis.
Mice with a high platelet count were identified in the third generation of an ENU mutagenesis screen and several different lines of thrombocytotic mice have been established. Subsequent breeding of one line has demonstrated that this mutation, called Plt2, is inherited in an autosomal recessive manner. Automated platelet counts for Plt2 homozygote mice were 1997±642x109/L (mean±2SD; n=51), 140% of those observed for wild-type mice (1487±372; n=56) and Plt2 heterozygote mice (1402±554; n=76). Analysis of Plt2 animals has shown increased numbers of megakaryocyte precursors (as measured by meg-CFC/5x105 cells to maximal cytokine stimulation) in the bone marrow (Plt2 40±20 compared to wild-type (WT) animals 28±8; n=7) and spleen (Plt2 16±6 compared to WT 8±3; n=7, p=0.01). Mature megakaryocytes were increased in frequency in bone marrow sections (Plt2 86.8±28.4 compared to WT 56.8±18.5) and demonstrate a similar maturation profile to control animals when their nuclear ploidy is measured by flow cytometry.
Reciprocal bone marrow transplantation experiments demonstrate that the thrombocytotic phenotype was observed in Plt2 homozygous recipients of either wild type or Plt2 homozygous bone marrow, but not observed in wild type recipients of Plt2 homozygous bone marrow. This data indicates that the Plt2 mutation is acting extrinsically on the haemopoietic system. Despite having an elevated platelet count, Plt2 mutant mice have inappropriately elevated serum thrombopoietin levels (Plt2 5420±2842; n=15) compared to controls (2947 ±2310; n=13; p&lt;0.0001).
Mapping experiments have excluded both thrombopoietin and the thrombopoietin receptor, c-mpl, as the mutated gene. Further experiments will aim to map this mutation, which may be a novel regulator of thrombopoietin.