bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non-Intensive AML/MDS Treatment with Low-Dose Decitabine Prior to Reduced-Intensity Conditioning (RIC) and Allogeneic Blood Stem Cell Transplantation of Older Patients.
Authors: Lübbert Michael , Bertz Hartmut , Rüter Björn H. , Mertelsmann Roland H. , Finke Jürgen 
Published: October 2019

Abstract
Patients (pts) undergoing allogeneic stem cell transplantation for AML or high-risk MDS usually receive standard induction chemotherapy first, with the goal of achieving a complete remission (CR) or at least best response to conventional chemotherapy. This disease control is often necessary to bridge the time needed for identifying an unrelated donor in case no sibling donor is available, although CR is no absolute prerequisite for successful allografting following RIC (Bertz et al., J Clin Onc21:1480, 2003). Recently, non-intensive treatment with low-dose azanucleosides has been developed for older pts with high-risk MDS. Low-dose Decitabine (DAC) shows a particularly interesting activity in inducing cytogenetic remissions (38%) in MDS pts with poor-risk cytogenetics. The role of DAC prior to allografting has not yet been determined. Here we report our single-center experience of 10 consecutive pts treated with low-dose DAC for MDS (n=5), CMML (n=2) or AML (n=3). The median number of DAC courses given was 3 (range 1–13), with CR and PR as best response in 4 and 1 pt respectively, stable or persistent disease in 4 and 1 pt, resp. Allografting was either done as consolidation at time of best response (n=4) or as salvage for relapsed/refractory disease (n=6). Median age at time of allografting was 65 years (range 63–71). After conditioning with either FBM (n=8) or Flu/2 Gy (n=2), pts were transplanted from either matched sibling (n=3) or unrelated donor (n=7). One pt died before engraftment on day +13 due to infection. The other 9 pts engrafted, and no unexpected toxicities were noted. 6/9 pts have died either due to relapse (n=3) or infection in CR (n=3). Three pts are alive in CR at the time of this report (+1, +10, +26 months following transplant). Prior to transplantation two of them were in PR and CR following 2 and 8 courses of DAC, respectively, one had progression of CMML after 5 courses. In conclusion, we show that RIC and allografting in older pts with myeloid neoplasia following DAC treatment is feasible, and no unexpected toxicities have occurred. DAC pretreatment can induce improvement or even remission with negligible nonhematopoietic toxicity, thus bridging the time period of donor search prior to allografting. The allogeneic option in these pts should be explored more often and response to DAC and transplant risk-assessment (comorbidities, performance status etc.) will likely be major determinants of optimal timing of allografting in this setting.
Graft Versus Host Disease after Granulocyte Infusion.
Authors: Barrenetxea Cristina , Zuazu Francisco J. , Bueno Javier , Julia Antonio , Diaz Jose L. 
Published: October 2019

Abstract
INTRODUCTION
Graft versus host disease (GVHD) occurs when immunologycally competent cells are introduced into an immunoincompetent host. GVHD refers to both the immunologic insult and the consequences to the organism. The leading cause of GVHD is hematopoietic cell transplantation (HCT), other causes like solid organ transplants, blood transfusions, and maternal-fetal transfusions also reportedly cause GVHD.
CASE
We present a 33 years old man, who was diagnosed in October 1997 of acute myeloid leukemia, treated with idarrubicin, etoposid and citarabine (IDICE), with complete remission; after that he received intensification treatment with mitoxanthrone and citarabine, and consolidation with an allogeneic HSCT from a sibling donor.
The chimerism was 100% of the donor since first month.
There wasn’t any important complications after HSCT; except a GVHD skin, resolved with corticoids.
Seven years after HCST, in November 2004, a routine control detected donor’s chimerism 34% with a medullar relapse. Leukemia characteristics were the same than the initials, and a new treatment with IDICE was administrated, showing no response, therefore, a second cycle was administrated.
One week after the first treatment fever appeared, which persisted besides large spectre antibiotics, so empiric antifungal treatment was added. Two months after the relapse the patient remained febrile, and skin lesions appeared in head, arms, legs, abdomen and oral mucosa. A biopsy was performed and diagnosed with Fusarium sp.
The neutropenia persisted, and the overall status was worsening, so we decided donor granulocyte infusions from two HLA identical sisters; ten days later, neutropenia disappeared, the bone marrow hadn’t blastic cells, and chimerism was 100% donor. A month later, new skin lesions appeared, the biopsy confirmed GVHD and severe liver affectation was also demonstrated by biopsy. It was treated with corticoids and cyclosporine, with rapid resolution.
The patient left hospital, and until now chimerism remains 100% donor with complete remission, without treatment for GVHD.
CONCLUSION: Graft versus Host disease is usually presented after hematopoietic stem cells infusion but other causes are been reported as lymphocytes infusion, where is not a rare event, and in other cases as granulocytes infusion as in our patient.
GVHD after granulocyte infusion is not a common complication even though it has to be taken in mind in patients that show skin or liver affectation after infusion.
Impact of Occult Hepatitis B Virus Infection in Hematopoietic Stem Cell Transplantation.
Authors: Chen Po-Min , Hsiao Liang-Tsai 
Published: October 2019

Abstract
Using sensitive PCR assays, lower titers of hepatitis B virus (HBV) DNA has been detected in surface antigen (HBsAg)-negative patients, i.e., occult HBV infection, especially for those from HBV-endemic area. The pathogenic role of occult HBV infection has been studied in patients with HIV and HCV infection; however, its impact on hematopoietic stem cell transplantation (HSCT) is not understood at present. To examine the prevalence of occult HBV infection and resulting hepatic events through the course of HSCT, allogeneic HSCT recipients (and their donors) who were negative to HCV infection and HBsAg-negative before transplantation and had an at least 12 months of follow-up after transplantation were enrolled for the study, with serial follow up of serum HBV-DNA, HBV serology, and liver function tests through the course of HSCT. Nested PCR with 3 independent sets of primers were used to detect pre-S/S, precore/core and X viral regions of HBV as previously described, and those reactive by at least two of the three PCR assays were considered to have occult HBV infected. The impact of pre-transplant occult HBV infection was evaluated in terms of post-transplant HBV infection after transplantation. Between 1995 and 2004, 60 HBsAg-negative pairs of allogeneic HSCT recipients and donors were enrolled, with the characteristics of recipients: median age of 30 years (9–59), F/M=20/40, diagnosis including 18 AML, 12 ALL, 18 CML, 4 NHL and 8 SAA, graft including 28 BM and 32 PBSC, and preparative regimens including 44 myeloablative (BUCY and CYTBI) and 16 nonmyeloablative (fludarabine, busulfan and ATG). At transplant, total 6 recipients (10%, 6/60) and 2 donors (3%, 2/60) in different transplant pairs were found to occult HBV infection as defined. With a median follow up of 28 months (from 12.5 to 72 months) after transplantation, three of those 6 recipients with pre-transplant occult HBV infection (of whom all their donors had no occult HBV infection) had HBsAg appearance after transplantation. Importantly, for those two HSCT in which only donors were found to have occult HBV infection, occult HBV was only transiently detected in their recipients immediately after transplantation with a paralleled and transient elevation of quantitative serum HBV-DNA, but there was no HBsAg appearance. For the other recipients who did not have pre-transplant occult HBV infection, three also had HBsAg appearance. In conclusion, the impact of occult HBV infection on HSCT is mainly derived from those existed in the recipients rather than those from the donors.
Cryptogenic Organizing Pneumonia Following Allogeneic Hematopoietic Stem Cell Transplantation.
Authors: Jinta Minako , Ohashi Kazuteru , Sakurai Chihiro , Nashima Yuho , Tsuji Masanori , Harada Kyoichi , Sakai Miwa , Yamashita Takuya , Akiyama Hideki , Sakamaki Hisashi 
Published: October 2019

Abstract
Although encouraging survival statistics are now reported after hematopoietic stem cell transplantation (HSCT), pulmonary complications occur in up-to half of patients after HSCT and are major causes of morbidity and mortality. In this study, we describe cryptogenic organizing pneumonia (COP) after allogeneic HSCT in our institution between January 1986 and December 2005. Charts and chest radiographs of 601 transplant recipients were retrospectively reviewed for COP. Total 12 cases of COP were observed (2.0%) at a median interval of 148 days after HSCT (range, 53–475 days). They presented low-grade fever, non-productive cough and dyspnea at the onset of COP. The initial antibiotics treatment did not ameliorate these symptoms, but all patients well responded to 0.5–1mg/kg of prednisolone. However, in 9 out of 12 patients, COP eventually flared-up after the tapering-off of steroid, but responded to the retreatment. Although 3 patients died, there was no death due to pulmonary failure and 5-year survival was 74.1%. In remaining 9 patients, there was no relapse of primary disease for which the patient underwent HSCT. The clinical features of 12 patients were similar in that they all received an irradiation containing conditioning and most patients had a history of acute graft-versus-host disease (GVHD). Furthermore, 8 patients had active chronic GVHD (6 extensive and 2 limited) at the onset of COP. These findings suggest that both the irradiation and allogeneic immune reaction may play a crucial role in the development of COP after HSCT. Moreover, the patients with COP might enjoy a relatively good prognosis due to low rate of relapse of primary disease through graft-versus-leukemia reaction, even though facing multiple episodes of disease exacerbation of COP.
Eight Cases of Leukemia Treated with HLA Haploidentical Related Bone Marrow Transplantation and Chinese Herbal Medicine.
Authors: Zhou Yuhong , Yu Rongxi , Ye Baodong , Lin Shengyun , Zheng Zhiyin , Luo Xiusu , Shen Jianping , Hu Zhiping , Cheng Junfa 
Published: October 2019

Abstract
Objective: To explore the feasibility of Chinese herbal medicine in haploidentical related allogeneic bone marrow transplantation (Allo-BMT) without T-cell depletion for the treatment of leukemia.
Methods: From 2003 to 2005, four patients with CML and four patients with AML received allo-BMT with grafts from 1 or 3 HLA antigen mismatched related donors. All patients were preconditioned with high dose Ara-c, cyclophosphamide (CY)and total body irradiation (TBI) or Busulfan (Bu). Donors were given G-CSF 250μg/d for seven days prior to marrow harvest. GVHD prevention regimen consisted of CSA, MTX, ATG, MMF and CD25-mab. Chinese herbal medicine was given orally to all patients after transplantation according to the theory (syndrome differentiation) of Traditional Chinese Medicine (TCM). One or 2 weeks after transplantation, TCM were given with the purpose to increase Qi and cultivate Yin, strengthen the function of Spleen and Stomach. At the time of bone marrow convalescence, about 1 month post transplantation, different TCM was prescribed for increasing Qi, cultivating Blood, strengthening the function of Kidney, and fasting distillation.
Results: All patients were successfully engrafted. The median days of granulocyte >0.5×109/L and platelet >20×109/L were 12 (10–14) and 20(18–25) days, respectively. Seven patients developed grade I-IVGVHD, with two of them advanced to grade IV gut and liver GVHD and died of concurrent infection eventually. Two patients developed hemorrhagic cystitis. Six patients were alive in a disease-free situation after median following-up of 20 (6–36) months.
Conclusion: The major histoincompatibility barriers in the haploidentical related donor/recipient allo-BMT could be successfully carried out with G-CSF stimulated donor bone marrow combined with GVHD preservation and Chinese Herbal Medicine. Our patients were treated with TCM to regulate immunity immediately after clearing out of their bong marrow; With this remedy method, we improved the curative effect of bone marrow transplant and this deserves further study with a well designed clinical trial.
Allogeneic Hematopoietic Stem Cell Transplantation in T-Cell Non-Hodgkin Lymphoma.
Authors: Dulley Frederico L. , Sturaro Daniel , Ruiz Milton A. , Chiattone Carlos , Saboya Rosaura , Barros Jose C. , Sarmento-Neto Jose P. , Amigo-Filho Jose U. , Piron-Ruiz Lilian , Pereira Juliana , Chamone Dalton A.F. 
Published: October 2019

Abstract
T-cell non-Hodgkin Lymphoma (T-NHL) are uncommon malignancies that represent approximately 10% of all NHL. With few exceptions T-NHL have generally been reported to have a worse prognosis compared with B-cell lymphomas. Standard therapy for most T-NHL still need to be defined. To elucidate the feasibility and efficacy, we retrospectively analysed the data of 11 patients who underwent allogeneic hematopoietic stem cell transplantation from July 1991 to july 2006. Five female and five male patients with a matched sibling donor and a female mismatched underwent a transplant. The median age was 22 years (16 – 34). Six patients were diagnosed as lymphoblastic T, two were anaplastic large cell, two were peripheral T-cell unspecified and one was NK/T extranodal nasal-type. One was in first hard remission, three in second remission, one in third complete remission, one in early first relapse, one in second partial remission and four had refractory disease. Six patients were conditioned with TBI + cyclophosphamide (CY-TBI) and five with busulfan 16 mg/kg and melphalan 140 mg/sqm (Bu-Mel). Graft versus host disease (GVHD) prophylaxis was done with cyclosporin and short course methotrexate for most of the cases. 63 % had acute GVHD grade I to III and 45% had chronic GVHD. Overall survival is 36%. Four of the 11 patients are alive, still in complete remission, after one year, 12 years, 14 years, and 15 years from transplantation. Two of these patients were conditioned with CY-TBI and two with Bu-Mel. Allogeneic transplant can be useful to treat advanced T-NHL patients.
A Distinct Pattern of Non-HLA Polymorphisms Predicts an Increased Risk for GvHD without Benefit of GvL in HLA Matched Sibling Transplants for Chronic Myeloid Leukemia (CML).
Authors: Dickinson Anne M. , Pearce Kim F. , Norden Jean , Neylor A. , Holler Ernst , Rocha Vanderson , Gluckman Eliane , Kolb Hans-Jochem , Hromadnikova Ilona , Sedlacek Petr , Niederwieser Dietger W. , Brand Ronald , Ruutu Tapani , Apperley Jane , Goulmy E.A.J.M. , Olavarria Eduardo , de Witte T.M. , Roosnek Eddy , Siegert Wolfgang , Gratwohl Alois 
Published: October 2019

Abstract
Non-HLA polymorphisms (NHP) influence risk of GVHD and outcome of allogeneic hematopoietic stem cell transplants (HSCT) however their influence on GvHD vs GvL remains to be defined. A cohort of 291 CML HLA matched sibling transplants with known clinical risk factors; eg stage of disease, gender mismatch (female donor/male recipient), patient age and time from diagnosis to transplant as defined by the EBMT risk score, were typed via SNPs or microsatellites for cytokines (IL-1Ra, IL-4, IL-6, IL-10, IFNγ, TNFα, TNFR 11), steroid hormone receptors (VDR and ERα) and NOD2/CARD15 mutations. TNFRII-196 allele R; IL-10 ATC/ACC; IL-1 Ra (allele 2) and IL-4T were significantly associated with survival using univariate analysis. Two clinical Cox proportional hazards models were generated for the statistical analysis and used as a basis for further development: (i) using the EBMT risk score as a single variable on an ordinal scale or (ii) using the individual clinical factors of the EBMT risk score as categorical variables. After step-wise variable selection using the significant genetic factors as candidates, the resulting multivariate models indicated that absence of TNFRII-196 R, i.e. down regulation of TNF in the recipient, absence of IL-10 ATC/ACC, i.e. intermediate IL-10 production in the donor and presence of IL-1Ra (allele 2) i.e. down regulation of IL-1 in the donor were associated with poor outcome. The addition of the genetic variables significantly improved the preferred model containing the EBMT risk score as a single variable. The Goodness of Fit of the models was assessed by Kaplan-Meier curves showing clinically relevant differences between good, intermediate and poor prognostic groups. The worst prognostic scores included the absence of ATA/ACC in the donor, evidenced by a steep change in survival probability. Relapse was associated with clinical factors; absence of female to male transplants; absence of bone marrow transplants and presence of T cell depletion but no significant association was found with genetic factors. This study suggests that distinct high risk patterns of NHP of patients and donors can be defined, which influences survival due to factors associated with an increased risk of GvHD without the potential benefit of increased GvL response. Data add to the clinical factors (eg age, sex, multiparity of the donor) where an unrelated donor might be the preferred choice compared to a high risk sibling donor.
The Serum M-Spike and Transplant Outcome in Patients with Multiple Myeloma.
Authors: Dingli David , Pacheco Jorge M. , Dispenzieri Angela , Hayman Suzanne R. , Kumar Shaji , Lacy Martha , Gastineau Dennis A. , Gertz Morie Abraham 
Published: October 2019

Abstract
Background: High dose therapy with autologous stem cell transplantation (HDT-ASCT) has prolonged survival in patients with multiple myeloma. Patients who achieve a complete response (CR) benefit the most from this form of therapy. Thus, achieving a CR is an important goal of therapy and it will be beneficial if the probability of achieving CR can be determined for any patient before transplant.
Patients and Methods: A large cohort of patients with myeloma who received HDT-ASCT at Mayo Clinic Rochester was studied. The impact of various demographic, clinical and laboratory characteristics relating to the patients and their disease acquired were studied for their impact on response to HDT-ASCT, especially CR. Patients with a serum M-protein <0.1g/dL were excluded. Response definitions were as defined by established criteria. Survival analysis was performed according to the Kaplan-Meier method while univariate and multivariate analyses were performed with the proportional hazards method. We utilized knowledge of the rate of M-protein production by myeloma cells together with the clearance of the protein to estimate the pre-transplant disease burden.
Results: We studied 224 patients with a median age of 56.5 years (32.6 – 71). Patients were transplanted a median of 8.7 months after diagnosis. Almost all patients had a response to HDT-ASCT and 78 (35%) achieved a CR. Those patients who achieved a CR had a longer time to progression (TTP) compared to those who did not achieve CR (Figure 1). The cohort was thus divided into two groups: patients who achieved CR and those that did not. The clinical and laboratory characteristics of the two groups were compared. Among the pre-transplant parameters tested, only the size of the serum M-spike was a predictor for CR (p<0.0001). A simple function that describes the probability of achieving CR based on the serum M-spike before HDT-ASCT is described. The estimated rate of tumor re-growth after HDT-ASCT in patients who obtain a CR and in patients who only get a partial response are presented.
Conclusions: The pre-transplant disease burden in myeloma is the main determinant of response to HDT-ASCT. The individual probability of achieving CR can be estimated from simple clinical parameters providing a quantitative risk assessment prior to such a high-risk procedure. There is significant expansion of myeloma cells after HDT-ASCT. The design of clinical trials may benefit from knowledge of the kinetic aspects of the disease.
Figure Figure
Initial Identification of a Mouse Human Factor IX-Specific CD8+ T-Cell Epitope.
Authors: Hoffman Brad E. , Herzog Roland W. 
Published: October 2019

Abstract
A significant complication associated with treatment of inherited protein deficiencies, such as hemophilia B, by gene replacement therapy is the potential for the activation of transgene specific B and T cells to the therapeutic protein, coagulation factor IX (F.IX). In addition to the potential for inhibitor formation as a result of MHC class II antigen presentation (CD4+ T cell-dependent activation of B cells, which may also be observed in conventional protein-based therapy), gene expression may lead to MHC class I presentation of F.IX-derived peptides to CD8+ T cells. Upon in vivo gene transfer, such immune responses to may elicit a cytotoxic T lymphocyte (CTL) response capable of destroying target cells that express the F.IX transgene product. Therefore, to better understand the role of F.IX-specific CD8+ T-cell responses, it is essential that MHC I-restricted CD8 T-cell epitopes be identified. Here, we used a peptide library consisting of 82 individual 15-mer peptides overlapping by ten residues that spans the complete human F.IX (hF.IX) protein to preliminarily identify a specific immunodominate CD8+ T-cell epitope. The peptides were pooled into groups, each containing 8–11 peptides to create a matrix of 18 pools, with each peptide represented in two pools. C3H/HeJ were immunized with 5×1010 vector genomes of E1/E3-deleted adenovirus expressing hF.IX (Ad-hF.IX) via intramuscular injection into the quadriceps. Nine days later, the harvested spleen and popliteal lymph node cells were pooled and evaluated for CD8+ T-cell responses by intracellular cytokine staining for IFN-γ after being stimulated for 5h with peptides or controls. The frequency of IFN-γ producing hF.IX-specific CD8+ T-cells was determined by flow cytometry. While 16 pools from Ad-hF.IX immunized C3H/HeJ mice showed no response above the frequency of mock-stimulated cells, lymphocytes from two overlapping pools demonstrated a ~2.5-fold increase in frequency of CD8+ IFN-γ+ cells. From these results we can conclude that peptide 74 (SGGPHVTEVEGTSFL) contains a CD8+ T cell epitope for C3H/HeJ mice (H-2k haplotype). Furthermore, splenocytes from naive mice failed to respond to any of the peptide pools. The amino acid sequence corresponding to peptide 74 is located within the catalytic domain of hF.IX. This finding is of particular interest, in that, we previously reported a peptide containing the immunodominate CD4+ T-cell epitope in C3H/HeJ is also located within the catalytic domain of hF.IX (Blood 108:408). The definitive identification of hF.IX-specific CD8+ epitopes will facilitate the evaluation of experimental gene therapy strategies in murine models by providing a reagent for in vitro stimulation of F.IX specific CD8+ lymphocytes. For example, we can now determine the efficiency of CD8+ T cell activation as a function of vector, route, and dose following in vivo gene transfer.