bluuebunny/crossref_metadata_2025_split huggingface dataset:
Erythrocytosis after Allogeneic Bone Marrow Transplantation in the Patients with Severe Aplastic Anemia.
Authors: Park Soo-Jeong , Han Chi-Wha 
Published: October 2019

Abstract
Severe aplastic anemia (sAA) is a bone marrow failure disorder which is mostly a consequence of immunologically mediated stem cell destruction. Stem cell transplantation (SCT) from a histocompatible sibling is a treatment of choice for this disease but major obstacles in success of allogeneic SCT include graft-versus-host disease (GVHD), graft rejection and treatment related toxicities.
We describe two cases of post-transplant erythrocytosis in severe aplastic anemia. About 5 years later, following HLA-matched sibling transplantation, the patients (45-year-old male and 43-year-old male) developed a sustained increase in hemoglobin (>17 g/dL) and hematocrit (> 50%), an increase in the frequency of headache, and new onset of dizziness and malaise. Laboratory findings demonstrated normal ranges of other blood components and serum erythropoietin level, and they did not have smoking or other drugs. Also, they did not have a hepatosplenomegaly or other organ diseases. We initiated a therapeutic phlebotomy program (400 ml q 2–4 weeks and then q 2–3 months for 5 years) in order to lower the hematocrit to available values (Hb < 14.5 g/dL), and to induce iron deficiency (Fig 1). Repeated phlebotomy resulted in a decrease in symptoms and a total volume of blood venesection is about 9,200 – 11,200 ml so far.
Figure 1. Hemoglobin change after bone marrow transplantations. Figure 1. Hemoglobin change after bone marrow transplantations.
Reduced Intensity Conditioning (RIC) Allogeneic Stem Cell Transplantation (allo-SCT) for Patients with Refractory or Relapsed Non-Hodgkin’s Lymphoma (NHL).
Authors: de Lavallade Hugues , Bouabdallah Reda , Faucher Catherine , Furst Sabine , El-Cheikh Jean , Vey Norbert , Stoppa Anne-Marie , Sainty Danielle , Arnoulet Christine , Xerri Luc , Cassier Philippe , Gastaut Jean-Albert , Blaise Didier , Mohty Mohamad 
Published: October 2019

Abstract
This study aimed to evaluate the role of RIC allo-SCT for relapsed or refractory non-Hodgkin’s lymphoma (NHL). We report here our experience in 25 consecutive patients transplanted in a single center for high grade (n=17) or follicular NHL (FL; n=8). In the high grade NHL group, median age was 46 (range, 24–63) years, and all 17 patients received 2 or more previous chemotherapy regimens prior to RIC allo-SCT. In addition, 12 patients (71%) had failed autologous SCT and 6 patients (35%) had chemoresistant disease at time of allo-SCT. Among the 8 patients transplanted for a heavily pretreated follicular NHL (FL), median age was 52 (range, 34–59) years and median number of prior lines of therapy was 3 (range, 2–5), with 3 patients (38%) having chemoresistant diseases and 4 patients (50%) relapsing after autologous SCT.
Among the 17 patients with aggressive high grade NHL, we compared the outcome of T-cell and B-cell aggressive NHL. With a median follow-up of 15.4 (range, 3.4-65.2) months, the cumulative incidence of non-relapse mortality was 6%, (95%CI, 0.3%-31%) and the Kaplan-Meier estimate of progression-free survival (PFS) was significantly higher in the T-cell as compared to the B-cell group (P= 0.03; 100% vs. 40% at 3 years).
In the FL group, the cumulative incidence of non-relapse mortality was 25% (95%CI, 3%–65%). Six patients (75%) showed objective disease response with complete remission (CR) occurring concomitantly to graft-versus-host disease, including one CR after donor lymphocytes infusion. With a median follow-up of 19 (range, 7–85) months, 6 patients from the FL group are still alive of whom 5 in CR.
We conclude that a potent graft-vs.-lymphoma (GVL) may be achieved in FL patients, even those with chemoresistant disease or who have relapsed after autologous SCT. In the high grade NHL group, strategies aiming to enhance the GVL effect (Rituximab-based RIC and/or Rituximab maintenance therapy) in the B cell subtype are still needed. However, RIC allo-SCT is a feasible and promising strategy for aggressive NHL, with particularly low toxicity, and T-cell aggressive NHL benefiting most from a potent GVL effect, likely overcoming the poor prognosis usually associated with this phenotype.
Reduced-Intensity Stem Cell Transplantation for Adult T-Cell Leukemia: The Results of a Second Multi-Center Prospective Study and the Impact of Antithymocyte Globulin on Early Relapse.
Authors: Uike Naokuni , Tanosaki Ryuji , Utsunomiya Atae , Choi Ilseung , Masuda Masato , Saburi Yoshio , Tomonaga Masao , Etoh Tetsuya , Hidaka Michihiro , Kannagi Mari , Harada Mine , Okamura Jun 
Published: October 2019

Abstract
As we previously reported(Blood, 2005;NST-1), allogeneic stem-cell transplantation from an HLA identical sibling donor with reduced-intensity conditioning(RIST) consisting of fludarabine(FL), busulfan(BU) and antithymocyte globulin(ATG) for adult T-cell leukemia(ATL) patients(pts) appears to be a feasible treatment modality. Disease relapse, however, was the main cause of treatment failure. We conducted a second phase 1 clinical trial of RIST for ATL pts without ATG(NST-2).
Objectives: We evaluated the safety and feasibility of RIST for ATL using the same conditioning regimen except that we did not use ATG.
Patients and Methods: Between September 2003 and January 2006, 14 pts ranged from 50 and 62 years of age were enrolled. After the conditioning regimen with FL 30 mg/m2/d on days -8 to -3, BU 4 mg/kg/d on days -6 to -5, they received G-CSF-mobilized PB stem cells. The primary end points were either engraftment, as evaluated by the achievement of complete donor chimerism(CC) before d90, or the occurrence of early transplant-related mortality(TRM) before d100.
Results: All 14 pts achieved CC before d90, while two pts died of TRM before d100, thus demonstrating the successful results for the primary end points. The incidence of severe acute GVHD(grade III-IV) was 21%. A disease relapse occurred in 6 pts from d30 to d775, 5 of whom eventually died of ATL. As of July 31, 2006, 6 pts are still alive, while 8 died of either ATL(5 pts) or TRM(3 pts). The event free and overall survivals(EFS, OS) at 2 years were 40% and 43%, respectively. Among the 12 evaluable pts, the HTLV-1 proviral load decreased to an undetectable level after RIST in 9 pts. Therefore, the results of CC before d90(14/14versus[vs]14/15*), TRM before d100(2/14vs2/15*), severe acute GVHD(3/14vs5/15*), disease relapse(6/14vs9/15*), 2 year-EFS (40%vs20%*) or -OS(46%vs33%*) and the anti-HTLV-1 effects(9/12vs8/15*) were closely comparable with those of NST-1*. The incidence of early disease recurrence before d100 tended to be low(21%[3/14]vs44%*[7/16]*), thus resulting in a longer mean survival time(804 days vs 262 days*) after RIST.
Conclusion: Our two studies(NST-1, NST-2) confirmed that, whether ATG was administered or not, RIST is considered to be a feasible treatment modality. Moreover, conditioning without ATG may improve the survival by delaying a disease relapse without increasing the severity of acute GVHD. A third study (phase 2 trial of RIST without ATG) is currently underway.
Fludarabine, Cyclophosphamide and ATG Based, Reduced Intensity Conditioning for HLA-Match Sibling Donor Transplant in Severe Aplasic Anemia (SAA) - Case Report.
Authors: Pawlowska Anna B. , Bolotin Ellen , Falk Peter , Forman Stephen , Rosenthal Joseph 
Published: October 2019

Allogeneic bone marrow transplantation (BMT) from an HLA-identical sibling is a curative form of therapy for patients with acquired severe aplastic anemia.
Survival has significantly improved over the past 3 decades. The actuarial risk of rejection has been reduced to about 7%. Improved results with survival in excess of 90% have been reported. Current preparative therapies are associated with early and late sequelae such as acute and chronic graft-versus-host disease (aGvHD or chGvHD, respectively) and secondary tumors. Two patients (6 years and 11 years old) with SAA, who had an HLA-identical sibling donor could not proceed with myeloablative therapy at the time of transplant due to delay in results of chromosome stability and fragility in one patient and abnormal pulmonary function in the second. Both received reduced intensity preparative regimen with Fludarabine (30 mg/m2×4 doses) Cyclophosphamide (5 mg/kg×4 doses) and rabbit ATG (1.5 mg/kg×4 doses) followed by an unmanipulated allogeneic BMT from their HLA-identical sibling donors. Graft versus host disease prophylaxis consisted of Cyclosporine from day -1 and Methotrexate 15 mg/m2 on day +1 and 10 mg/m2 on days +3, +6, +11 after transplant. Myeloid engraftment occurred on day +15 and day +28. The time to a platelet count >20,000 unsupported was +11 days and +29 days. No transplant-related toxicities, including mucositis or alopecia, were recorded. There were no signs for aGvHD or chGvHD. The patients continue with full donor chimerism 27 months and 130 days post transplant, respectively. This data suggests that a non-myeloablative, immunosuppressive regimen is sufficient to provide a stable engraftment in the patients with SAA. This approach may be associated with decreased transplant-related short- and long-term toxicities. A larger study is needed to fully evaluate the outcome and the toxicity associated with this conditioning.
Comparison of Therapeutic Effect between Related Donor and Unrelated Donor Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) in the Treatment of Leukemia.
Authors: Liu Qifa , Yang Kai , Fan Zhiping , Sun Jing , Xu Dan , Wei Yongqiang , Zhang Yu , Meng Fanyi 
Published: October 2019

Abstract
Objective : To compare the effect for leukemia between related donor hematopoietic stem cell transplantation (RD-HSCT) and unrelated donor hematopoietic stem cell transplantation (URD-HSCT).
Methods: 115 patients received allo-HSCT, of whom 68 received RD-HSCT and 47 received URD-HSCT. All patients are HLA serologically matched. Total body irradiation (TBI) plus cyclophosphamide (CTX) was adopted in 56 cases and modified BuCY conditioning regimen (busulfan, Ara-C, Cyclophosphamide) in 59 cases. T and B cell reconstitution at different time points was assayed by flow cytometer in one year after transplantation. GVHD and nonage infection are observed after transplantation. The diference of haematopoietic and immunological reconstitution between the two groups are estimated with Independent-Samples T test. Kaplan-Meier survival analysis model is used to estimate the overall survival and the disease-free survival (DFS) in two groups.
Results: The time in WBC>1.0×109/L are +13.09±2.39 and +16.28±3.01d(P=0.003), the time in BPC>20×109/L are +14.91±6.62 and +20.21±7.29d(P=0.042), respectively, in related donor bone marrow transplantation (RD-BMT) and unrelated donor bone marrow transplantation (URD-BMT). The time in WBC>1.0×109/L are +12.47±2.96 and +13.13±4.09d(P=0.488), the time in BPC>20×109/L are +12.16±4.24 and +15.67±7.12d(P=0.020), respectively, in related donor peripheral blood stem cell transplantation (RD-PBSCT) and unrelated donor peripheral blood stem cell transplantation (URD-PBSCT). The reconstitution of CD4+CD3+ at 1, 3, 6, 9, 12months and CD45RA+CD4+ at 1 month, and CD8+CD3+ at 3 months were different significantly between RD-HSCT and URD-HSCT(P value was 0.001, 0.017, 0.029, 0.041, 0.015, 0.015, 0.043, respectively). The incidence of II~IV°acute GVHD(aGVHD), chronic GVHD(cGVHD) and the lethality of GVHD are 45.45% and 52.27%(P=0.560), 45.31% and 63.16%(P=0.102), 6.06% and 15.91%(P=0.112), respectively, in RD-HSCT and URD-HSCT groups. The relapse rate are 18.18% and 11.36%(P=0.424), respectively, in RD-HSCT and URD-HSCT groups. The incidence of nonage infection are 42.42% and 47.73% (P=0.696), respectively, in RD-HSCT and URD-HSCT groups.The overall survival and the disease-free survival rate at three-year were 67.80±6.90% and 61.60±7.70%(P=0.133), 62.30±6.90% and 56.80±7.90%(P=0.177), respectively, in RD-HSCT and URD-HSCT groups.
Conclusion The therapeutic effect for leukemia is not different between RD-HSCT and URD-HSCT.
A Novel Plasmodium falciparum Microneme Protein Interacts with Host Band 3 during Red Cell Invasion.
Authors: Li Xuerong , Chen Huiqing , Oh Steven S. , Chishti Athar H. 
Published: October 2019

Abstract
Clinical manifestation of Plasmodium falciparum malaria is directly linked to the blood stage of the parasite life cycle. At the blood stage, circulating merozoites invade red blood cells (RBCs) through multiple receptor-ligand interactions that mediate a complex series of events in a period of approximately one minute. Certain strains of P. falciparum favor an invasion mechanism that depends on sialic acid residues on the host RBC surface, while other strains favor a sialic acid-independent mechanism to invade RBCs. Two putative non-glycosylated extracellular regions of human RBC band 3 termed, 5ABC and 6A, function as an invasion receptor binding the 42 kDa C-terminal processing product of P. falciparum merozoite surface protein-1 (MSP142) and its 19-kDa secondary processing product (MSP119) by a sialic acid-independent mechanism. Earlier, we reported screening of a P. falciparum cDNA library in a yeast two-hybrid system, which led to the identification of P. falciparum merozoite surface protein 9 (MSP9) as another parasite surface protein that interacts with the 5ABC receptor region of band 3. MSP9 formed a co-ligand complex with MSP142 and/or MSP119 in their native forms. Here, we present identification of a novel P. falciparum microneme protein from the previous cDNA library screen. Primary sequence analysis of a positive clone in the library screen revealed a cDNA fragment in the correct open reading frame of a novel P. falciparum gene of 1,221 bps, encoding a hypothetical protein of 406 amino acids. Further sequence analysis predicted it is a membrane protein transversing the lipid bilayer multiple times. Anti-peptide antibody raised against a predicted non-membrane domain recognized a single band at ~49 kDa (calculated mass, 46.9 kDa) from the P. falciparum protein extract by Western blotting. Protein co-localization studies that employed established markers for the merozoite surface, rhoptries, and micronemes by an indirect immunofluorescence assay suggested that the ~49 kDa protein was expressed in micronemes at trophozoite/schizont stages. Immunoelectron microscopy demonstrated that the 49 kDa protein is indeed localized primarily to micronemes in the merozoites. Based on our characterization, we have tentatively named this novel protein as microneme-associated membrane antigen 1 (MAMA1). Functional studies demonstrate that the MAMA1 antibody blocked RBC invasion by P. falciparum (3D7 strain) in vitro, in a concentration-dependent manner. Furthermore, MAMA1 presumably embedded in small vesicles present in the parasite protein extract bound to intact human RBCs, and the MAMA1-RBC binding was neuraminidase and trypsin resistant, but chymotrypsin sensitive. Native MAMA1 bound specifically to the 5ABC peptide of band 3 in our solution binding assay. Together, these results suggest that the novel microneme protein MAMA1 interacts with host band 3 and facilitates merozoite entry during RBC invasion.
Correction of Immunodeficiency Associated with NEMO Mutation by Umbilical Cord Stem Cell Transplantation Using a Reduced-Intensity Conditioning Regimen.
Authors: Tono Chikako , Takahashi Yoshihiro , Terui Kiminori , Sasaki Shinya , Kamio Takuya , Tandai Satoru , Sato Tomohiko , Kudo Ko , Toki Tsutomu , Tachibana Naoki , Yoshioka Takakazu , Nakahata Tatsutoshi , Morio Tomohiro , Nishikomori Ryuta , Ito Etsuro 
Published: October 2019

Abstract
X-linked recessive anhidrotic ectodermal dysplasia with immunodeficiency (XL-EDA-ID) is a developmental and immunologic disorder caused by hypomorphic mutations in the nuclear factor-κB essential modulator (NEMO) gene. NEMO is the regulatory subunit of the IκB kinase (IKK) complex, which phosphorylates and degrades NF-κB inhibitor α (IκBα), causing NF-κB activation. Following the identification of amorphic NEMO mutations causing familial incontinentia pigmenti (IP), hypomorphic mutations in NEMO have been identified in XL-EDA-ID patients. Affected boys are susceptible to infections with various microorganisms, mostly pyogenic bacteria and mycobacteria. Stem cell transplantation (SCT) is thought to be the only curative treatment, but successful SCT has not yet been reported. We here report the first successful treatment of the disorder by SCT. The patient was a 3-year-old boy. His mother and maternal grandmother had been diagnosed with IP. He had frequent episodes of enterocolitis, and Enterobacter aerogenes sepsis. Mutation analysis revealed NEMO mutation (1167 insC) in both the patient and his mother. Flow cytometry analysis showed lower NEMO expression in each PBMC lineage, and CD40L induced less up-regulation of CD23, CD54, CD86, and CD95 in the patient’s cells. The patient did not have an HLA-matched related or unrelated bone marrow donor. At 3 years of age, an unrelated UCSCT was performed after written consent was obtained from his parents. Pretransplant conditioning consisted of fludarabin (30 mg/m2/d) from day -7 to day -3, melpharan (70 mg/m2/d) from day -6 to day -5, and rabbit anti-T-lymphocyte globulin (ATG) (2.5 mg/kg/d) from day -5 to day -1. The patient received 4.6 × 107 total nucleated cells/kg from a male donor. The recipient and donor were one antigen mismatched by serology and four loci mismatched by DNA typing. Following uneventful engraftment, NEMO protein expression was normalized and cytokine response was significantly improved. Lineage-specific genetic analysis confirmed full donor chimerism. Six months after UCSCT, the patient is in perfect performance status. This outcome shows that correction of immunodeficiency associated with NEMO mutation is possible by SCT, and UCSCT with a reduced-intensity regimen can be a suitable therapy for affected patients.
Autologous Stem Cell Transplantation (ASCT) for Poor Prognosis Non Hodgkin Lymphomas (NHL).
Authors: Nese Martha C. , Guillermo Cecilia , Isaurralde Hugo , Diaz Lilian , Topolansky Laura , Zunino Juan , Perdomo Susana , Perdomo Ana , Lavagna Graciela , Diaz Andrea , Stevenazzi Mariana , Baubeta Alberto 
Published: October 2019

Abstract
Between 1995 and 2005, we performed 329 hematopoietic stem cell transplantation (HSCT), 286 autoulogous and 43 allogeneic.
Long term results of treatment and outcome of ASCT in 100 Non Hodgkin Lymphoma (NHL) were analyzed. Median age was 47 years (range18 – 64) and the histology was: Follicular Lymphoma 15%, diffuse large B cell lymphoma (DLBCL) 47%, T lymphoma 27% and 11% others. At diagnosis 66% had advanced stage (III/IV), 40% had B symptoms, and 34% had extranodal involvement. Disease status at HSCT was: 5 % primary induction failure, 41% CR1, 20% CR2 +, 7% CRU, 12% relapsed. Number of prior chemotherapy regimens was 47% 2 lines, 20% 3 lines and 3% 4 lines; 27% had received prior induction or consolidation radiotherapy. Condition regimens consisted of BEAC (81%), BEAM (15%), others (4%). Stem cell source: 39% received BM + PBSC and 61% PBSC.
Sixty nine are alive with a median survival of 3448 days (9.5 years). Median overall survival was similar in DLBCL (59%) and peripheral T lymphoma (60%). The best overall survival was observed in CR1 (77%) versus 52% in CR2 and 66% in PR1. Primary cause of death was relapsed or progression (24/31).
We concluded that high dose therapy and autologous HSCT is an effective therapy for patients with poor risk NHL however relapse continues to be the most common cause of treatment failure. Newer strategies such as monoclonal antibody, require further investigation but early reports appear promising in reducing relapses in autologous HSCT.
Maintenance Therapy with Low Dose Thalidomide, Dexamethasone and Clarithromycin (Biaxin) (BLT-D) Following Autologous Transplant (ASCT) for Multiple Myeloma (MM).
Authors: Holmberg Leona A. , Brandvold Aurora , Bensinger William I. 
Published: October 2019

Abstract
Relapse remains a major problem after a standard ASCT for MM. Strategies to prevent relapse have included post transplant maintenance therapy. M Coleman et al (Leukemia and Lymphoma43:1777–1782, 2002) pioneered a regimen of BLT-D to treat in a non-transplant setting MM and reported a high CR/PR response rate (93%). Since the BLT-D regimen showed significant disease response, it seemed reasonable to study this regimen as maintenance therapy after ASCT. Between 7/2003–1/2006, 23 patients (stage II, n=6 and stage III (n=17) were treated. 26% of patients had poor prognostic cytogenetics. 61% had elevated beta 2 microglobulin at initial diagnosis; 30% still had elevated beta 2 microglobulin at time of ASCT. 48% of the patients had received Thalidomide therapy before ASCT. All were conditioned for ASCT with melphalan 200 mg/m2. 30–120 days after recovery from the acute toxicity of ASCT, patients were treated with Biaxin 250 mg po bid, Dexamethasone 20 mg po q week and Thalidomide beginning at 50 mg po daily for 14 days, then increased to 100 mg po daily. After one year of combination therapy, Biaxin and Dexamethasone were stopped and Thalidomide was continued as long as tolerated or until disease progression. The median time to starting therapy was 102 days (range 40–120) post ASCT. Neuropathy was the most common toxicity. Four patients stopped therapy because of significant peripheral neuropathy and four patients required dose reduction of Thalidomide because of neuropathy. Eight patients had reduction in Dexamethasone dosing because of toxicity. One patient stopped Biaxin for rash. Number of infections seen included pneumonia (n=3), viral upper respiratory infection (n=2), sinusitis (n=1) and bronchitis (n=3). One patient withdrew from therapy to undergo elective second ASCT. Three patients have died: infection (n=1), MM progression (n=1) and complications of second ASCT (n=1). In patients who still had detectable MM after ASCT prior to beginning BLT-D therapy, 46% of the evaluable patients to date have been shown to go into complete remission on BLT-D therapy. Three patients have progressed. 18 (78%) out of 23 patients remain alive without disease progression. Median follow-up is 20.5 months (range 6–25). Further follow-up is needed to determine the effect of BLT-D upon relapse and survival of MM ASCT patients.