bluuebunny/crossref_metadata_2025_split huggingface dataset:
Germinal Center B Cell and Non-Germinal Center B Cell-Like DLBCL Have Similar Clinical Features at the Time of Progression and Comparable Outcome Following Autologous HSC Transplantation.
Authors: Costa Luciano J. , Feldman Andrew L. , Micallef Ivana N. , Inward David J. , Johnston Patrick B. , Porrata Luis F. , Litzow Mark R. , Ansell Stephen M. 
Published: April 2020

Abstract
Background: Germinal center B cell-like (GCB) DLBCL, as determined by gene expression profiling or immunohistochemistry, is more likely to be cured by initial conventional chemoimmunotherapy than non-germinal center B cell-like (non-GCB) DLBCL. For patients with relapsed or refractory chemosensitive DLBCL, high-dose chemotherapy and autologous hematopoietic stem cell (HSC) transplant is considered standard-of-care treatment, but it is unknown whether the outcome of these patients is similarly influenced by the subtype of DLBCL. We therefore explored the differences between patients with GCB and non-GCB DLBCL as regards their clinical features at relapse after first line therapy and their outcome following salvage autologous HSC transplant.
Methods: Patients undergoing BEAM conditioning and autologous HSC transplantation for relapsed or refractory chemosensitive DLBCL at Mayo Clinic, Rochester, MN between 2001 and 2006 were included. Immunohistochemical analysis was performed for CD10, BCL-6 and MUM1 allowing classification in GCB and non-GCB-like DLBCL, as well as for BCL-2. GCB and non-GCB groups were compared in terms of known prognostic factors at time of progression and outcome after HSC transplant
Results: Fifty-nine patients were included and had retrievable tumor samples to allow immunohistochemical analysis. Median follow-up of survivors was 25 months; median age at the time of transplant was 60 years (range 17–77); All patients had failed at least one previous anthracycline-based regimen (15 had refractory disease). Overall, 25/59 cases (42%) were positive for CD10, 32/58 (55%) for BCL-6, and 19/58 (32%) for MUM1. Thirty-two patients (54%) were classified as having GCB and 27 (46%) non-GCB-like DLBCL. Patients in the GCB and non-GCB group had similar time to progression (TTP) (median 12.5 months vs. 11 months, Wilcoxon P=0.81) after first line therapy and similar IPI-R scores (Chi-square, P=0.38). In univariate analysis, GCB and non-GCB did not differ in time to relapse after HSC transplant (log rank test P=0.77) or survival (log rank test P=0.48; figure). The lack of demonstrable difference in survival persisted even after correction for IPI-R and TTP, factors know to affect transplant outcome (Cox regression, RR=0.80 for GCB; P=0.28). BCL-2 was highly expressed in both GCB (81%) and non-GCB (96%) and did not correlate with outcome in the entire population nor in any of the two groups.
Conclusion: Patients with chemosensitive relapsed or refractory GCB and non-GCB-like DLBCL derive similar benefit from autologous HSC transplant.
Figure Figure
No Significance of Derivative Chromosome 9 Deletion on the Clearance Kinetics of BCR/ABL Fusion Transcripts, Cytogenetic or Molecular Response, Loss of Response or Treatment Failure to Imatinib Mesylate Therapy for Chronic Myeloid Leukemia.
Authors: Kim Dong Hwan (Dennis) , Sriharsha Lakshmi , Kamel-Reid Suzanne , Chang Hong , Messner Hans , Lipton Jeffrey 
Published: April 2020

Abstract
Background: Deletion of the derivative chromosome 9 (der 9; del-der9) is a poor prognostic factor in chronic myeloid leukemia (CML) patients treated with hydroxyurea or interferon. However, its prognostic implication in imatinib mesylate (IM) treated patients is unclear. One study reported that IM improved but did not fully reverse the poor prognosis of CML patients with del-der 9, while another suggested that IM might overcome the poor prognostic significance of del-der 9. The purpose of current study is to evaluate the prognostic implication of del-der 9 in CML patients in terms of hematologic, cytogenetic and molecular responses, loss of response to IM and IM treatment failure rate in addition to BCR/ABL mRNA quantitative PCR monitoring.
Methods: The current study included 163 CML patients with available FISH results using the LSI-BCR/ABL-(ES) probe (Vysis, IL, USA) treated at the Princess Margaret Hospital (Toronto, Canada). End points of the study included hematologic response (HR), major or complete cytogenetic response (CyR; MCyR/CCyR), major or complete molecular response (MoR; MMoR/CMoR), loss of response (LOR), treatment failure (including primary hematologic or cytogenetic resistance and LOR), progression to accelerated phase or blast crisis (AP/BC), or time to IM dose escalation to achieve further response or to overcome LOR.
Results: Of 163 patients, 22 (13.5%) had del-der 9 prior to initiation of IM. No differences were noted between those with and without del-der 9 in terms of disease phase or additional cytogenetic abnormalities. No differences were noted for the time to HR (p=0.598), MCyR (p=0.281), CCyR (p=0.883), MMoR (p=0.125), or CMoR (p=0.834). Times to LOR (p=0.974), treatment failure (p=0.455), progression to AP/BC (p=0.276), or dose escalation of IM (p=0.816) were not significantly different between those with and without del-der 9. The serial monitoring of BCR/ABL mRNA quantitative PCR showed similar patterns of BCR/ABL mRNA reduction between the 2 groups.
Conclusion: The presence of del-der 9 in CML patients prior to IM therapy does not influence:
the response to IM therapy in terms of HR, CyR and MoR; LOR, treatment failure or progression to AP/BC; and time to dose escalation of IM.
Therefore, from the clinical point of view, the presence of del-der 9 does not impact on the management of CML patients treated with IM.
Figure 1. No differences of complete cytogenetic response rate (A) or major molecular response rate between patients with versus without deletion of derivative chromosome 9 after imatinib mesylate therapy Figure 1. No differences of complete cytogenetic response rate (A) or major molecular response rate between patients with versus without deletion of derivative chromosome 9 after imatinib mesylate therapy
Prognostic Impact of Deletions of Derivative Chromosome 9 on Patients (pts) with Chronic Myelogenous Leukemia (CML) in Chronic Phase Treated with Nilotinib or Dasatinib.
Authors: Quintás-Cardama Alfonso , Kantarjian Hagop , Thomas Deborah , Koller Charles , Shan Jenny , Cortes Jorge 
Published: April 2020

Abstract
Background: Submicroscopic deletions of the derivative chromosome 9 [del der(9)] mapping to regions adjacent to the translocation breakpoints occur in 9% to 15% of patients with CML. Deletion of der(9) is powerful prognostic indicator associated with an unfavorable prognosis in patients treated with interferon-alpha (IFN-α)-based therapies. Imatinib is currently the standard treatment for patients with CML and it appears to overcome the adverse prognostic impact imparted by deletions of der(9).
Methods: We tested the prognostic impact of the deletions of der(9) in 323 patients with CML treated at our institution with the 2nd generation tyrosine kinase inhibitors (TKIs) nilotinib (n=144) or dasatinib (n=179). The presence of deletions of der(9) was investigated by FISH analysis using the LSI-BCR/ABL-(ES) probe (Vysis, Downers Grove, IL) in 244 patients. The median age was 55 years (range, 15–83) and the median follow-up was 18 months (range, 1–44). The primary endpoints evaluated were survival, complete hematologic response (CHR) and cytogenetic responses.
Results: Twenty-eight (12%) patients were found to have del der(9) and 216 an intact der(9). Among patients with deletions, 16 were in chronic phase (CP), 8 in accelerated phase (AP), and 4 in blast phase (BP) at the start of nilotinib or dasatinib therapy. In the group of patients without deletions, 112 were in CP, 54 in AP and 50 in blastic phase (BP). Overall, 222 (91%) of 244 patients were assessable for response. There was no significant difference between patients with or without deletions regarding the rate of CHR, major (MCyR) or complete (CCyR) cytogenetic responses, and event-free (EFS), and overall (OS) survival at 12 months for the total population.
CML Phase deletion der(9) [No. Patients] CCyR (%) p EFS (12 months) p OS (12 months) p No (112) 72 1 84 0.2 97 0.01 Chronic Yes (16) 73 78 92 Not Done (30) No (54) 31 0.7 54 0.22 69 0.62 Accelerated Yes (8) 38 75 88 Not Done (27) No (50) 24 1 9 0.56 30 0.56 Blastic Yes (4) 25 25 25 Not Done (22)
Among pts in CP there was no difference in response rate or EFS, but pts without del der(9) had an improved OS at 12 months compared with those carrying der(9) (97% vs 92%; p=0.01). There appears to be no significant difference between pts treated with nilotinib and those treated with dasatinib.
Conclusion: Our results suggest that although the outcome of patients with CML treated in AP or BP with either nilotinib or dasatinib does not differ regardless of their deletion status, those in CP carrying del der(9) deletions may have a worse overall survival than their counterparts without deletions. This is in contrast to what has been reported with imatinib therapy. The reason for this difference is unclear.
Long-Term Ultra-Low-Dose Acyclovir Against Varicella-Zoster Virus Reactivation after Allogeneic Hematopoietic Stem Cell Transplantation.
Authors: Asano-Mori Yuki , Kanda Yoshinobu , Oshima Kumi , Kako Shinichi , Shinohara Akihito , Nakasone Hideki , Sato Hiroyuki , Watanabe Takuro , Hosoya Noriko , Izutsu Koji , Asai Takashi , Hangaishi Akira , Motokura Toru , Chiba Shigeru , Kurokawa Mineo 
Published: April 2020

Abstract
Varicella-zoster virus (VZV) infection remains a common complication after hematopoietic stem cell transplantation (HSCT). The introduction of long-term prophylaxis with low-dose acyclovir against VZV reactivation has been investigated, because VZV-related complications including post-herpetic neuralgia and secondary infection significantly affect the patient’s quality of life. We started long-term oral acyclovir at 200 mg/day in July 2001. Acyclovir was continued until the end of immunosuppressive therapy and at least one year after transplantation. To evaluate the efficacy of this long-term prophylaxis with ultra low-dose acyclovir against VZV reactivation, we analyzed the records of 242 Japanese adult patients who underwent allogeneic HSCT for the first time from June, 1995 to November, 2006 at University of Tokyo Hospital. Sixty-six patients developed VZV reactivation at a median of 248 days after HSCT, with a cumulative incidence of 34.7%. There was no VZV-related death. Only one breakthrough reactivation occurred during long-term acyclovir, responding well to the therapeutic dose of valacyclovir. The use of long-term acyclovir was the only independent determinant that significantly decreased the overall incidence of VZV reactivation (20.4% vs 50.5%, P&lt;0.0001). As for VZV-related complications, only post-herpetic neuralgia was seen in three patients with long-term prophylaxis, whereas serious complications including CNS involvement, motor neuropathy and ophthalmic complications were involved in 14 without long-term prophylaxis. Eleven of 16 patients with long-term prophylaxis were treated as outpatients, whereas 39 of 50 patients without long-term prophylaxis required hospitalization (hospitalization 31% vs 78%, P=0.0015). Fifteen of the 57 patients who discontinued long-term acyclovir developed VZV reactivation at a median of 147 days after the discontinuation of acyclovir, with a cumulative incidence of 32.1%. VZV reactivation following discontinuation predominantly occurred in patients who were receiving immunosuppressive therapy at the cessation of acyclovir (44% vs 20%, P=0.12). These findings suggest that long-term prophylaxis of ultra-low-dose acyclovir resulted in a successful prevention of severe VZV-related symptoms and death, with a significantly decreased overall incidence of VZV reactivation. With this prophylaxis, visceral dissemination and serious complications other than post-herpetic neuralgia were completely eliminated, and thereby need for hospitalization was significantly reduced. To continue acyclovir for patients with profound immunosuppression might be important to further decrease the overall incidence of VZV reactivation.
Figure Figure
Prospective Measurement of BK Virus Blood and Urine Levels, and Associations with Morbidity, in Recipients of Allogeneic Hematopoetic Stem Cell Transplants.
Authors: O’Donnell Peter H. , Swanson Kate , Josephson Michelle A. , Artz Andrew S. , Rich Elizabeth , Stock Wendy , van Besien Koen 
Published: April 2020

Abstract
BK virus (BKV) is an important pathogen and cause of nephropathy in recipients of renal transplants, but its clinical significance in patients following hematopoetic stem cell transplantation (HSCT) is less well described. Over a 10 month period we prospectively measured BKV (by quantitative PCR) in the blood and urine of 103 patients who had undergone previous allogeneic HSCT [HLA-identical donor (n = 58), alternative donor (HLA-mismatched-related, matched-unrelated, or cord) (n = 45)] and who were receiving inpatient or outpatient post-transplant care. The median time from transplantation to the last follow-up virus sampling was 422 days (range = 12 to 3456 days), and the cohort included patients undergoing transplants as early as 1998 through 2007. BK viruria was manifest at any time during the period of measurement in 62% of the patients. Only 16% (16/103) developed BK viremia. All patients with BK viremia also had detectable BK viruria. In 38 patients who underwent BKV monitoring beginning immediately after transplant, development of BK viruria was an early phenomenon (median 26 days post-transplant, range = 4 to 274 days), while BK viremia occurred later (median 157 days post-transplant, range = 62 to 323 days). More recipients of alternative donor transplants compared to HLA-identical transplants developed BK viruria (75% vs 53%, P = 0.03) and BK viremia (24% vs 9%, P = 0.02). Given the tropism of BKV for the genitourinary tract and its association with hemorrhagic cystitis, urinalyses from all patients were analyzed for the presence and number of red blood cells (RBCs). Those patients with microscopic hematuria (81/103) had significantly higher levels of urinary BKV than patients without hematuria (P &lt; 0.001), and there was a suggestion that the degree of hematuria was directly related to the amount of urinary virus, since a subset of patients with more pronounced hematuria (&gt; 5 RBCs per high-powered microscopic field) had higher levels of urinary BKV than those with only small numbers of urinary RBCs (P = 0.06). Blood BKV levels were not associated with hematuria. The presence of BK viremia and/or viruria were not significantly associated with renal function, as measured by the mean serum creatinine, although 2/16 patients with BK viremia developed biopsy proven BKV interstitial nephritis, with one requiring hemodialysis. In summary, BK viruria is a common early finding in patients undergoing allogeneic HSCT, especially in those who do not have HLA-identical donors. Our data support the claim that BKV urinary infection is associated with hematuria post-HSCT. BK viremia occurs later and less commonly. Investigation of a larger number of patients is warranted to establish the incidence of and risk factors for BKV nephropathy in the allogeneic HSCT setting.
Once Daily Busulfan Cyclophosphamide Is Well Tolerated and Effective Prior to Allogeneic Hematopoietic Stem Cell Transplantation.
Authors: LeMaistre Julia A. , Bachier Carlos , Smith Brad , LeMaistre C.F. , Shaughnessy Paul J. 
Published: April 2020

Abstract
The development of intravenous busulfan (Bu) allowed for the delivery of a standard daily dose of Bu to be given in one dose instead of dividing 4 times per day. Pharmacokinetic (PK) studies of Bu support the feasibility of once daily dosing and prior clinical studies found no unexpected toxicity of once daily Bu when combined with fludarabine. Based on this data we began an institutional protocol of delivering Bu once daily follwed by standard cyclophosphamide (Cy) and allogeneic hematopoietic stem cell transplantation (HCT). Only limited data in the literature describes toxicity and clinical outcomes of once daily BuCy. We report a retrospective review of our institutional data using once daily BuCy vs 4x daily BuCy and total body irradiation (TBI)/Cy in pts who received allogeneic HCT from January 2000 to December 2006. Bu 3.2mg/kg daily × 4 days followed by Cy 60mg/kg daily × 2 days was given to 42 patients (pts). Bu 0.8mg/kg/dose given 4x daily for 4 days followed by Cy 60mg/kg was given to 15 pts. Cy 60mg/kg daily for 2 days and fractionated TBI 1200 cGy delivered over 3 days was given to 60 pts. All donors were HLA matched at A, B, C, DR, and DQ and were related/unrelated in 23/19, 11/4, and 21/39 in the once daily BuCy, 4x daily BuCy, and TBI/Cy, respectively. Significantly more pts with myeloid leukemias received a BuCy regimen and significantly more pts with lymphoid malignancies received TBI/Cy. Median follow up for all pts was 370 days. VOD developed in 2 pts in the once daily BuCy group, 1 pt in the 4x daily BuCy group, and in no pts in the TBI/Cy group. Acute GVHD grade II-IV occured in 33% of the once daily BuCy pts, 53% of the 4x daily BuCy pts, and 32% of the TBI/Cy pts. Estimated actuarial transplant related mortality (TRM) and survival are described in the table below. There was no statistical difference in TRM or survival between the once daily and 4x daily BuCy groups or the total BuCy group and TBI/Cy group. The once daily BuCy group had significantly less TRM than the TBI/Cy group at 100 days (p=0.04) and at 1 year (p=0.01). The once daily BuCy group also had significantly better survival at one year compared to the TBI/Cy group (p=0.01), but this became non-significant at 3 years. The significant differences in the pt populations treated in the BuCy and TBI/Cy groups, as well as the retrospective nature of this study, limit the ability to draw conclusions comparing the groups. However, this review does demonstrate once daily BuCy and allogeneic HCT is well tolerated with no unexpected TRM, and provides good long term survival in pts with myeloid malignancies.
Survival and TRM 1xBuCy (95%CI) 4xBuCy (95%CI) Cy/TBI (95%CI) 100 day TRM 7% (1–16%) 21% (7–51) 22% (15–35) 1 year TRM 21% (11–38) 37% (17–69) 45% (33–59) 1 year Survival 70% (53–82) 47% (21–69) 49% (35–61) 3 year Survival 43% (24–59) 27% (8–50) 37% (24–49)
Comparison of Outcomes of Bone Marrow and Umbilical Cord Blood Transplants from Unrelated Donors in Adult Patients with Acute Myeloid Leukemia/Myelodysplastic Syndrome.
Authors: Masuoka Kazuhiro , Miyakoshi Shigesaburo , Ishiwata Kazuya , Tsuji Masanori , Takagi Shinsuke , Yamamoto Hisashi , Kato Daisuke , Matsuhashi Keiko , Seo Sachiko , Matsuno Naofumi , Uchida Naoyuki , Wake Atsushi , Yoneyama Akiko , Taniguchi Shuichi 
Published: April 2020

Abstract
&lt;Objectives&gt; Promising results of cord blood transplants from unrelated donors have been reported in adults. To compare of outcomes of bone marrow transplants (BMT, n = 51), and umbilical cord blood transplants (UCBT, n = 110) from unrelated donors in adult patients with acute myeloid leukemia (AML) / myelodysplastic syndrome (MDS), we analyzed retrospectively the results of 161 adult patients with AML and MDS in our hospital.
&lt;Patients and Methods&gt; We reviewed medical records of 161 patients with AML/MDS who had received a hematopoietic stem cell transplant from an unrelated donor between August 2000 and April 2007 at Toranomon Hospital, Tokyo, Japan.
&lt;Results&gt; Patient’s median age was 55 years (17–71). Diagnoses include de novo AML (n =85), MDS overt AML (n=48), refractory anemia (RA) (n=13), and refractory anemia with excess of blasts (RAEB) (n=15). Disease status consisted of standard (CR1 of AML and RA, n=30) and advanced (other status, n=131). Recipients of UCBT had more advanced disease than recipients of BMT at the time of transplantation (89 percent vs. 65 percent, P&lt;0.001). The median number of nucleated cells that were infused was 0.26×108 per kilogram of the recipient’s body weight for cord blood and 2.5×108 per kilogram for bone marrow (P&lt;0.001). The major difference were higher number in the UCBT group of HLA mismatches (defined by serology for class 1 and molecular typing for DRB1).The donor was HLA mismatched in 96% of UCBT recipients, and in 41% of BMT recipients (P&lt;0.001). Other significant differences were observed in preparative regimens, and graft-versus-host disease (GVHD) prophylaxis. Nonadjusted estimates of 2-year OS and DFS rates were 53% and 48% in the BMT group, and 33% and 25% in the UCBT group (P&lt;0.001). However, 2-year OS and DFS rates in the standard group were not significantly different in the two groups (63% and 63% in the BMT group, and 75% and 58% in the UCBT group; p=0.98 and 0.32). Compared with BMT recipients, UCBT recipients had delayed hematopoietic recovery (Hazard ratio [HR]= 0.52; 95% confidence interval [95CI]: 0.36–0.75; p&lt;0.001), increased 100 day TRM (HR=3.07; 95CI 1.45–6.51; p&lt;0.01) and decreased grade II–IV acute graft-versus-host disease (aGVHD) (HR=0.58; 95CI 0.35–0.96; p=0.03). Two-year relapse rate was not significantly different in the two groups.
&lt;Conclusion&gt; We conclude that UCBT from an unrelated donor is a therapeutic option for adult AML/MDS patients who lack an HLA-identical donors. Higher mortality, especially from non-relapse causes, is the biggest problem to be solved to increase the feasibility of this approach.