bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Hematopoietic Cell Transplantation Comorbidity Index: No Effect on Outcome of Reduced-Intensity Allografts.
Authors: Frankfurt O. , Altman J. , Krishnamurthy J. , Evens Andrew M , Gordon L. , Singhal S. , Tallman M. , Williams S. , Winter J. , Duffey S. , Singh V. , Meagher R. , Mehta J. 
Published: April 2020

Abstract
The hematopoietic cell transplantation-comorbidity index (HCT-CI) has been proposed as a means to estimate the risk of transplant-related mortality (TRM) and the likelihood of overall survival (OS) after allogeneic HSCT. However, its value and applicability remain unclear; in a 2-center study, it was predictive of outcome at one but not at the other in multivariate analysis (Blood2007;110:4606).
We investigated the effect of HCT-CI in 130 adult patients with hematologic malignancies undergoing reduced-intensity HSCT after 100 mg/m2 melphalan (+ 50 mg/kg cyclophosphamide if no prior autograft). GVHD prophylaxis comprised cyclosporine/tacrolimus and MMF. 18% of the donor-patient pairs were 1 antigen/allele-mismatched. 57% had refractory disease. 45% had failed an autograft. ECOG performance status (PS) was 0–34%, 1–48%, 2–14%, and 3–4%. The HCT-CI score distribution was 0–10%, 1–4%, 2–28%, 3–24%, 4–15%, 5–10%, 6–8%, and ≥7–2%. Overall, the patient population had higher HCT-CI scores than described in other studies (Cancer2008;112:1992).
In multivariate analysis, TRM was higher with HLA mismatch and PS 2-3, and OS was lower with PS 2-3, HLA mismatch, refractory disease, donor age &gt;45 y, elevated LDH, and platelets &lt;100.
HCT-CI 0 vs 1-2 vs ≥3 had no effect on TRM or OS. HCT-CI 0-2 vs ≥3 had a borderline effect on TRM (P=0.09) and OS (P=0.15) in univariate analysis, but no effect in multivariate analysis when forced into the model with factors known to be significant. No significant correlation was seen between HCT-CI and any of the factors found to be predictive of outcome.
Figure Figure
Because serum albumin is a powerful non-specific predictor of general health and outcome in all clinical situations, we hypothesized that it would correlate with the PS. As shown in the figure below, it did. We expected that it would correlate with HCT-CI because increasing comorbidity should theoretically be associated with declining albumin. However, it did not.
Figure Figure
In our experience, HCT-CI does not correlate with outcome – especially when other pertinent factors are taken into account. Since most data supporting HCT-CI have originated from a single center, it is possible that its applicability depends on individual centers and the treatment protocols employed. However, lack of correlation of HCT-CI with albumin does call its biological plausibility into some question. HCT-CI cannot be employed unless refined and validated prospectively in multi-center studies.
Febrile Reactions Occurring with Second Cycle of High Dose Melphalan and Stem Cell Transplantation in Patients with AL Amyloidosis: A “Melphalan Recall” Reaction.
Authors: Rosenzweig Michael , Seldin David C. , Remick Daniel G , Skinner Martha , Quillen Karen , Oran Betul , Finn Kathleen T. , Sanchorawala Vaishali 
Published: April 2020

Abstract
Systemic AL amyloidosis is a clonal plasma cell disease related to multiple myeloma characterized by the wide spread deposition of amyloid fibrils into tissues and organs. Treatment for this disease is directed towards reducing amyloidogenic monoclonal light chains by attacking the underlying plasma cell dyscrasia. Aggressive treatment with high dose intravenous melphalan followed by autologous stem cell transplantation (HDM/SCT) is effective in inducing hematologic and clinical remissions and in extending survival. Tandem cycles of HDM/SCT have been shown to increase hematologic complete response (HCR) rates in patients with multiple myeloma and have therefore been included in the treatment of AL amyloidosis. Between April 1994 and July 2008, 57 patients with AL amyloidosis at Boston University Medical Center were treated with a second cycle of HDM/SCT after failing to achieve a HCR following a first transplantation. Eleven of 57 patients (19%) treated with tandem transplantation developed a high fever; 12-24 hours following melphalan administration. Other clinical features noted in some of the patients include hypotension, acute renal failure, and skin rash. Among the 11 patients described, there were 7 men and 4 women. The average age was 53.5 years (range 41-60). The average peak temperature of the 11 patients was 39.1º C (range, 38.1-39.4°C). All patients experienced resolution of fever within 24–48 hours. Six of the 11 patients developed a rash and 5 developed hypotension that was responsive to intravenous fluids or pressors when indicated. Two of the patients developed acute renal failure that improved following resolution of the fever. In all 11 patients, workup for an infectious etiology of fever was negative. One of the 11 patients described, had cytokine measurements before, during and after the febrile reaction. The concentration of several pro-inflammatory as well as anti-inflammatory cytokines increased significantly. IL-6, a classic endogenous, pyrogenic cytokine, increased 10 fold with this reaction demonstrating a clear physiologic response correlating with the clinical findings. Therefore, an unusual febrile reaction mediated by pyrogenic cytokines can occur in patients with AL amyloidosis exposed to a second cycle of high dose melphalan. While this reaction has not been observed in patients with multiple myeloma treated in similar fashion for unclear reasons, clinicians should be aware of this phenomenon we have termed a “melphalan recall” reaction in patients with AL amyloidosis treated with tandem cycles of HDM/SCT.
Outcome after Allogeneic Stem Cell Transplantation for Adult Acute Myeloid Leukaemia Patients Exhibiting Isolated or Associated Trisomy 8 Chromosomal Abnormality: A Survey on Behalf of the Acute Leukemia Working Party (ALWP) of the EBMT.
Authors: Chevallier Patrice , Labopin Myriam , Nagler Arnon , Ljungman Per T. , Verdonck Leo , Volin Liisa , Zander Axel , Finke Jürgen , Socie Gerard , Cordonnier Catherine , Harousseau Jean-Luc , Mohty Mohamad , Rocha Vanderson 
Published: April 2020

Abstract
Trisomy 8 (+8) is one of the most common chromosomal abnormality encountered in acute myeloid leukemia (AML), occurring in about 10 to 15% of cases. Currently, data assessing specifically the role of allogeneic hematopoietic stem cell transplantation (allogeneic-HSCT) in the setting of AML with +8 are still relatively sparse. The aim of this multicenter retrospective analysis was to perform a survey on overall outcomes after allogeneic-HSCT of AML patients harboring +8 as a sole chromosomal abnormality or associated with other abnormalities. We have identified 182 de novo AML patients who underwent allogeneic-HSCT between 1990 and 2007 exhibiting isolated +8 (n=136) or +8 associated to other favorable (n=8), intermediate (n=30), high-risk (n=7) or unknown (n=1) group cytogenetics reported to the EBMT. Median age was 37 years. At transplant 108 (59%) patients were in first complete remission (CR). The donor was HLA identical sibling in 115 (63%) and peripheral blood HSCT was used in 54% (n=98). Conditioning regimen was myeloablative in 82%. With a median follow-up of 48 months, 5-year non-relapse mortality (NRM), relapse rate (RR), LFS and OS were 25%, 30%, 45% and 47%, respectively. Five-years OS and LFS was not significantly different between AML patients with isolated or associated +8 (44% vs. 56% P=0.14 and 41% vs. 55%, P=0.11). In a multivariate analysis, LFS rate was improved when patients were female and transplanted in CR with an HLA identical sibling donor. LFS rate were 62% and 64% when using an HLA identical sibling donor in patients in CR1 and CR2/CR3, respectively. Isolated or associated +8 were not a risk factor for any outcomes (OS, LFS, RR, NRM). We conclude that allo-HSCT, from an HLA identical sibling donor, appears to be the treatment of choice for AML patients in CR at transplant with isolated or associated +8.
Allogeneic Transplantation (HCT) for Myelodysplastic Syndrome:Recent MDACC Experience.
Authors: Popat Uday , de Lima Marcos J , Ativitavas Touch , Rondon Gabriela , de Padua Silva Leandro , Koca Ebru , Zhang Weiqing , Alousi Amin , Anderlini Paolo , Giralt Sergio A. , Hosing Chitra M. , Jones Roy , Kebriaei Partow , Khouri Issa , Nieto Yago , Qazilbash Muzaffar H. , Andersson Borje S. , Champlin Richard 
Published: April 2020

Abstract
BACKGROUND: Many recent advances have occurred in the field of MDS including hypomethylating agents, lenalidomide, and WHO classification. Likewise the field of HCT has also undergone major new developments including non ablative conditioning, better supportive care, better HLA typing, selection of unrelated donors and development of reduced toxicity ablative regimens like Busulfan and Fludarabine. The role of HCT therefore needs to be redefined in light of these developments. The purpose of this study is to report our recent results.
PATIENTS AND METHODS: 89 consecutive patients with MDS as defined by WHO criteria treated at our institution between Jan 2002 and April 2008 are included in this report. There were 60 males and 29 female with a median age of 54 (23–67). There were 5(6%) patients with RA, 1(1%) RARS, 9(10%) RCMD, 22(25%) RAEB 1, 17(19%) RAEB 2, and 35(39%) therapy related MDS(t MDS). Their IPSS scores were 25(28%) patients with Intermediate 1, 49(55%) Intermediate 2, 15(17%) high. Their WPSS categories were 5(6%) patients Low, 9(10%) Intermediate, 49(55%) high, and 26(29%) very high. 51(57%) patients had a matched related donor and 38(43%) had an unrelated donor. Conditioning regimen were Flu/Bu in 56(63%) patients, Bu/Cy 1(1%), Flu/Mel 32(36%). According to HCT-CI index, the comorbidity scores were 0 in 16(18%) patients, 1 or 2 in 19(21%) and greater then 2 in 54(61%). Median time from diagnosis to transplant was 8 months (range 1–51 months).
RESULTS: With a median follow up of 28 (3–73) months, 2 year overall(OS) and disease free survival were 54%(95% CI; 42%–66%) and 52%(95% CI; 40%–64%) respectively. Cumulative incidence of non relapse mortality at 2 years was 23% (95% CI; 16%–35%). Cumulative incidence of relapse mortality at 2 years was 23% (95% CI; 15%–34%). As per WHO grouping, OS was 63%, 60%, 46% and 48% in patients with Low blast count (RA, RARS, RAMD), RAEB1, RAEB2 and t MDS( p=0.46) respectively. WPSS score was significantly(P=0.01) predictive of overall survival (see fig): 27% surviving in very high risk group, 61% in high risk group and 78% in Low and intermediate risk group. Likewise cytogenetic risk group and IPSS were significantly predictive of survival. Donor type or graft source did not predict outcome. Five patients developed primary(3) or secondary(2) graft failure. Median time to neutrophil engraftment was 13 days (8–26 days) and to platelet engraftment was 16 days (9–89 days).
CONCLUSION: These results in patients with comorbidities and with a median age of 54 years are promising. Cytogenetics and prognostic scores based on cytogenetics predict outcome after HCT.
Figure Figure
Rituximab Containing Autologous Stem Cell Transplantation May Be Curative in Mantle Cell Lymphoma for Patients in First Remission, but Not for Patients with Recurrent Disease.
Authors: Tam Constantine S , Bassett Roland , Ledesma Celina , Korbling Martin J. , Okoroji Grace-Julia , Harrell Robyn , Hsu Yvonne , De Padua Silva Leandro , Alousi Amin M. , Hosing Chitra M , Kebriael Partow , Rondon Gabriela , Giralt Sergio , De Lima Marcos , Anderlini Paolo , Popat Uday , Qazilbash Muzaffar H. , Samuels Barry , Champlin Richard E , Khouri Issa F 
Published: April 2020

Abstract
In order to determine if the addition of rituximab (R) had changed the outcome of autologous stem cell transplantation (AUTO) in patients with mantle cell lymphoma (MCL), we examined the outcome of 86 patients transplanted at the MD Anderson Cancer Center, in first partial or complete remission (frontline AUTO, n=50) or for relapsed / refractory disease (salvage AUTO, n=36).
&lt;&lt;&lt;FRONTLINE AUTO&gt;&gt;&gt; Among frontline patients, 29 were transplanted in the pre-R era (AUTO-R), and 21 in the post-R era (AUTO+R). AUTO-R patients received homogenous treatment with hyper-CVAD induction and Cy- TBI conditioning. AUTO+R patients were treated with R-hyper-CVAD, hyper-CVAD and R-CHOP induction in 62%, 10% and 29% respectively, and R-Cy-TBI and R-BEAM conditioning in 43% and 52% respectively. Median age (range) at transplantation was 57 (42–66) and 56 (38–73) for the AUTO-R and AUTO+R groups respectively (p=0.91); other baseline characteristics including sex, time from diagnosis, performance status, stage, B-symptoms, B2m, LDH and MIPI were similar. Prior to transplantation, CR or unconfirmed CR (CRu) was present in 38% and 57% of AUTO-R and AUTO+R patients respectively (p=0.18), and 33 of 34 patients were negative on Gallium/PET scan. Following transplantation, CR/CRu was achieved in 93% and 100% patients respectively (p=0.50). Progression free survival (PFS) was similar between AUTO-R and AUTO+R patients for the first 2 years. However, after 2 years a clear difference emerged on the PFS curve with no relapses occurring among 9 AUTO+R patients followed between 30 and 96 months. In contrast, AUTO1-R patients experienced a continuous pattern of relapse (p=0.03 compared with AUTO+R patients). For patients remaining in remission at 2 years, no deaths had occurred in the AUTO+R group, whereas 15 of 22 AUTO-R patients had died.
&lt;&lt;&lt;SALVAGE AUTO&gt;&gt;&gt; The 36 salvage patients had similar baseline characteristics as frontline patients, except for the proportion of patients with chemosensitive disease (100% vs 86%, p=0.01) and negative Gallium/PET scans (97% vs 71%, p=0.01), favoring the frontline group. In contrast to the results of frontline patients, no difference was observed in salvage patients by the use of R (p=0.52 and 0.50 for PFS and OS respectively).
&lt;&lt;&lt;CONCLUSION&gt;&gt;&gt; Autologous transplantation with rituximab has the potential to cure a proportion of patients with MCL, but only if performed during the first remission. Patients transplanted beyond first remission continued to experience a poor prognosis.
Figure Figure
Immune Reconstitution Following Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation: The Impact of Expanding CD28negCD8+ T-Cells on Relapse.
Authors: Yakoub-Agha Ibrahim , Saule Pasquine , Salleron Julia , Cracco Pascale , Coiteux Valerie , Magro Leonardo , Dufosse Francoise , Bruno Benedicte , Jouet Jean-Pierre , Duhamel Alain , Dessaint Jean-Paul , Labalette Myriam 
Published: April 2020

Abstract
Allogeneic stem cell transplantation has become standard therapy for haematological malignancies through the positive immunologic graft-versus-leukaemia effect. Initial immune recovery relies on peripheral expansion of infused T-cells which switch to a memory-like phenotype. This study prospectively investigated whether changes in subset composition precedes late complications after myeloablative HLA-matched transplantation. Of 80 recipients, 51 experienced neither early infection nor acute graft-versus-host disease (GVHD), of whom 18 were still free of clinical complication throughout 395 – 1564 days of follow-up. Compared with this complication-free subgroup, patients who developed chronic GVHD as the only event recovered similar numbers of circulating T-cells with predominance of CD8+ T-cells lacking CC-chemokine receptor-7 and CD28 expression. Conversely, poor CD8+ T-cell recovery with diminished numbers of CD28neg CD8+ T-cells (~1/4th of that of relapse-free patients) preceded occurrence of relapse. In multivariate analysis, lower CD28neg CD8+ T-cell counts by day 60 were associated with greater risk of subsequent relapse (HR 0.33; 95% CI 0.14 - 0.76; P = 0.01). Enumeration of CD28neg CD8+ T-cells in patients without early clinical complication could assist in predicting risk of relapse and help build an algorithm for accelerating the immune recovery by reducing the immunosuppressive regimen and considering the introduction of prophylactic donor lymphocyte infusions.
Gene Expression Differences Between Fetal Liver-Derived and Adult Bone Marrow-Derived Murine Megakaryocyte Progenitors: Implications for DS-TMD.
Authors: Wieland Karen , Cantor Alan B. 
Published: April 2020

Abstract
About ten percent of infants with Down syndrome are born with a transient myeloproliferative disorder (DS-TMD) that spontaneously resolves within the first few months of life. Twenty to thirty percent of these infants subsequently develop acute megakaryoblastic leukemia (DS-AMKL), typically within a year or two following resolution of their DS-TMD. Recent work has shown that both DS-TMD and DS-AMKL cells harbor acquired mutations in the key megakaryocyte transcription factor GATA-1 that lead to the exclusive production of a short GATA-1 isoform (GATA-1s). The mechanism by which GATA-1s acts in DS-TMD/AMKL remains incompletely understood. Mice engineered to produce only GATA-1s exhibit hyperproliferation of fetal liver-derived megakaryocytes, but normal growth of post-natal bone marrow-derived megakaryocytes. This suggests that unique microenvironmental features of fetal liver compared to bone marrow differentially influence the effects of GATA-1s on megakaryopoiesis. In order to further understand the mechanisms involved in these stage-specific effects, we compared gene expression profiles of wild type megakaryocyte progenitors (MkPs) isolated directly from embryonic day 13.5 (e13.5) murine fetal liver (FL) and from adult bone marrow (BM). Cells were FACS sorted based on the immunophenotype lin-sca-1-c-kit+ CD41+ CD150+, which has recently been shown to mark megakaryocyte-selective progenitors. Colony forming assays of the sorted cells revealed 92–100% growth of megakaryocyte colonies in culture medium containing multilineage cytokines (SCF, IL3, IL11, GM-CSF, EPO and TPO), confirming strong enrichment for megakaryocyte lineage cells. RNA from sorted FL and BM MkPs was then used to perform Affymetrix 3′ cDNA expression microarray analysis. Expression of early-stage megakaryocyte factors, such as c-mpl, FOG1, GATA1, Runx-1 and Fli-1 were found in both sets of samples, confirming selection of megakaryocyte progenitor cells. Importantly, we observed a striking up regulation of interferon alpha (IFN alpha) inducible genes belonging to the p200 family in BM MkPs compared to FL MkPs. Gene set enrichment analyses (GSEA) confirmed broad up regulation of the IFN alpha pathway, and as well up regulation of the JAK-STAT pathway in BM MkPs compared to FL MkPs. These findings were validated by quantitative RT-PCR and in situ immunohistochemistry. Given that STAT1 is a direct GATA-1 target gene and a major downstream effector of IFN alpha signaling, we hypothesize that enhanced IFN alpha signaling in the bone marrow may compensate for potential deficiencies of STAT1 during fetal liver megakaryopoiesis in the setting of GATA-1s. Experiments are underway to test this hypothesis.
Platelets Having a W127X Mutation in GPIX Express Sufficient Residual Amounts of the GPIbα Chain to Support Ristocetin-Mediated Agglutination and Adhesion to VWF and Collagen Under Conditions of Flow.
Authors: Kanaji Taisuke , Takata Yuka , Moroi Masaaki , Seki Ritsuko , Oku Eijiro , Sano Masayuki , Nakazato Sachie , Izuhara Kenji , Sueoka Eizaburo , Imamura Yutaka , Okamura Takashi 
Published: April 2020

Abstract
A W127X mutation in platelet glycoprotein (GP)IX is the most common genetic defect in Japanese Bernard-Soulier Syndrome (BSS). Patients having this mutation are often misdiagnosed as having immune thrombocytopenia (ITP) because of residual expression of GPIbα on the platelet surface. The purpose of the present investigation was to determine whether the residual amount of GPIbα present on the surface of GPIXW127X BSS platelets might be sufficient to support adhesive functions of the GPIb complex. Flow cytometric analysis of platelets from our GPIXW127X BSS patient revealed 7–11% of the normal level of GPIbα (3,700 receptors/platelet), although the expression of GPIbα estimated by western blot analysis was only 1% of normal. Expression levels of other receptors such as GPIIb, GPVI, and α2 integrin were 3–4 times higher per platelet than that of normal controls–probably due to the increased size of the BSS platelets. To characterize the ability of GPIXW127X BSS platelets to bind VWF, we evaluated their agglutination in the presence of various concentrations of ristocetin, and found that ristocetin-induced agglutination was absent at 1.2 and 1.5 mg of ristocetin/ml, but present at 2.0 mg/ml. We then evaluated the ability of GPIXW127X BSS platelets to adhere under conditions of flow to immobilized VWF, type 1 collagen, and type III collagen. Whereas platelets derived from a Type I BSS patient having a TGTG deletion within the GPIbα gene in which GPIbα is completely absent (Thrombosis and Haemost 77:1055,1997) were unable to adhere to immobilized VWF under conditions of high shear, GPIXW127X BSS platelets bound well, demonstrating that the residual amount of GPIbα present GPIXW127X BSS platelets is sufficient to mediate adhesion to VWF. Finally, recent studies (J Thromb Haemost 5:797,2007) have shown that platelet adhesion to Type III collagen can be mediated by either interaction of GPIbα with VWF, or by interaction of the integrin α2β1 with collagen under high shear flow. In support of this notion, adhesion of GPIbαTGTG del BSS platelets to immobilized Type III collagen could be completely inhibited by addition of the anti-α2β1 blocking mAb, Gi9, while adhesion of GPIXW127X BSS platelets to Type III collagen was only marginally affected. Taken together, we conclude that
platelets having a W127X mutation in GPIX express residual amounts of functional GPIbα, and both GPIb-VWF and integrin α2β1-collagen interactions are physiologically important under conditions of high shear stress.
Residual expression of GPIbα in GPIXW127X platelets, therefore, likely accounts for the relatively mild bleeding phenotype in this variant form of BSS.