{"title":"Predicting Immuno-Metabolic Complications After Allogeneic Hematopoietic Cell Transplant with the Cytokine Interleukin-33 (IL-33) and its Receptor Serum-Stimulation 2 (ST2).","authors":"Uttam K Rao, Brian G Engelhardt","doi":"10.2991/chi.d.200506.002","DOIUrl":"https://doi.org/10.2991/chi.d.200506.002","url":null,"abstract":"<p><p>Patients undergoing allogeneic hematopoietic cell transplantation (HCT) are at risk for numerous acute and long-term complications from this procedure. Post-transplant diabetes mellitus (PTDM) is a common but under-recognized problem. Similar to graft-<i>versus</i>-host disease (GVHD), new-onset diabetes is characterized by immune dysregulation that can negatively impact transplant outcomes. This review will discuss the biology of IL-33/ST2 in acute GVHD and PTDM development, and how this cytokine axis could be leveraged for predicting and treating immuno-metabolic complications after transplant.</p>","PeriodicalId":10368,"journal":{"name":"Clinical Hematology International","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b3/44/CHI-2-3-101.PMC8432328.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39476333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Maintenance Strategies Post-Autologous Stem Cell Transplantation for Newly Diagnosed Multiple Myeloma.","authors":"Sarah A Bird, Graham H Jackson, Charlotte Pawlyn","doi":"10.2991/chi.d.200502.001","DOIUrl":"https://doi.org/10.2991/chi.d.200502.001","url":null,"abstract":"<p><p>Multiple myeloma, the second most common hematological malignancy worldwide, has demonstrated dramatic improvements in outcome in the last decade. In newly diagnosed patients, induction chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard of care. After ASCT, the majority of patients experience disease remission but, despite recent therapeutic developments, most will eventually relapse. In this review we consider clinical aspects of maintenance therapies that can be used post-ASCT to prolong remission duration. We discuss the evidence for the effectiveness of each of these drugs as a maintenance therapy, alongside other benefits and drawbacks to their use, for example, route of administration and potential toxicities. We discuss questions which remain unanswered around the optimal use of currently available maintenance therapies and review newer agents being considered for use as maintenance such as emerging immunotherapies.</p>","PeriodicalId":10368,"journal":{"name":"Clinical Hematology International","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fb/9b/CHI-2-2-59.PMC8432350.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39477345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Practicing Clinical Hematology During the COVID-19 Outbreak: A Challenge Like No Other.","authors":"Mohamad Mohty, Arnon Nagler, Bipin Savani","doi":"10.2991/chi.d.200506.001","DOIUrl":"10.2991/chi.d.200506.001","url":null,"abstract":"","PeriodicalId":10368,"journal":{"name":"Clinical Hematology International","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f5/cd/CHI-2-2-41.PMC8432345.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39477342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Raheel Iftikhar, Qamar Un Nisa Chaudhry, Tariq Mehmood Satti, Syed Kamran Mahmood, Tariq Ghafoor, Ghassan Umair Shamshad, Nighat Shahbaz, Mehreen Ali Khan, Tariq Azam Khattak, Jahanzeb Rehman, Muhammad Farhan, Saima Humayun, Humera Haq, Syeda Ammaara Anwaar Naqvi, Faiz Anwer, Humayoon Shafique Satti, Parvez Ahmed
{"title":"Comparison of Conventional Cyclophosphamide <i>versus</i> Fludarabine-Based Conditioning in High-Risk Aplastic Anemia Patients Undergoing Matched-Related Donor Transplantation.","authors":"Raheel Iftikhar, Qamar Un Nisa Chaudhry, Tariq Mehmood Satti, Syed Kamran Mahmood, Tariq Ghafoor, Ghassan Umair Shamshad, Nighat Shahbaz, Mehreen Ali Khan, Tariq Azam Khattak, Jahanzeb Rehman, Muhammad Farhan, Saima Humayun, Humera Haq, Syeda Ammaara Anwaar Naqvi, Faiz Anwer, Humayoon Shafique Satti, Parvez Ahmed","doi":"10.2991/chi.d.200426.001","DOIUrl":"https://doi.org/10.2991/chi.d.200426.001","url":null,"abstract":"<p><p>Allogeneic stem cell transplant for high-risk aplastic anemia (AA) yields inferior results using conventional cyclophosphamide (CY)-based conditioning. The use of fludarabine (Flu)-based regimens has resulted in improved outcomes in high-risk patients. Limited data are available comparing these two conditioning regimens in such patients. We retrospectively analyzed 192 high-risk patients undergoing matched-related donor transplantation from July 2001 to December 2018. The median age was 19.5 (2-52) years. Patients were divided into 2 groups, Cy<sup>200</sup> anti-thymocyte globulin (ATG)<sup>20</sup> (Gp1 n = 79) or Flu<sup>120-150</sup> Cy<sup>120-160</sup> ATG<sup>20</sup> (Gp2 n = 113). The risk of graft failure was significantly higher in Gp1, and the majority occurred in patients with >2 risk factors (<i>p</i> = 0.02). The incidence of grade II-IV acute graft <i>versus</i> host disease (GVHD) and chronic GVHD was not significantly different between the two groups. The overall survival (OS) of the study cohort was 81.3 %, disease-free survival (DFS) 76.6 % and GVHD-free relapse-free survival (GRFS) was 64.1%. DFS and GRFS were significantly higher in Gp2 as compared to Gp1: DFS 84.1% <i>versus</i> 68.4 % (<i>p</i> = 0.02), GRFS 77.9% <i>versus</i> 54.4% (<i>p</i> = 0.01), respectively. We conclude that Flu-based conditioning is associated with superior OS, DFS and GRFS as compared to the conventional Cy-based regimen in high-risk AA.</p>","PeriodicalId":10368,"journal":{"name":"Clinical Hematology International","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e5/10/CHI-2-2-82.PMC8432348.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39477347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Bortezomib, Lenalidomide and Dexamethasone as Induction Therapy Prior to Autologous Transplantation in Multiple Myeloma: The More Is Likely the Better.","authors":"Mohamad Mohty, Florent Malard, Ali Bazarbachi","doi":"10.2991/chi.d.200507.001","DOIUrl":"10.2991/chi.d.200507.001","url":null,"abstract":"","PeriodicalId":10368,"journal":{"name":"Clinical Hematology International","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/54/a2/CHI-2-2-92.PMC8432347.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39477348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bhagirathbhai Dholaria, Yenny Alejandra Moreno Vanegas, Nancy Diehl, Aaron C Spaulding, Sue Visscher, Han W Tun, Sikander Ailawadhi, Prakash Vishnu
{"title":"Cost Analysis of R-CHOP <i>Versus</i> Dose-Adjusted R-EPOCH in Treatment of Diffuse Large B-Cell Lymphoma with High-Risk Features.","authors":"Bhagirathbhai Dholaria, Yenny Alejandra Moreno Vanegas, Nancy Diehl, Aaron C Spaulding, Sue Visscher, Han W Tun, Sikander Ailawadhi, Prakash Vishnu","doi":"10.2991/chi.d.200410.001","DOIUrl":"https://doi.org/10.2991/chi.d.200410.001","url":null,"abstract":"<p><p>Dose-adjusted rituximab, etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (DA.R-EPOCH) is used for upfront treatment of high-risk diffuse large B cell lymphoma (DLBCL). In this study, we compared the outcomes in patients with high-risk DLBCL who received frontline rituximab, cycophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) or DA.R-EPOCH immunochemotherapy. Outcomes and treatment-related cost were analyzed. DLBCL with one of the following features were included in the study: <i>MYC</i> ± <i>BCL2</i> or <i>BCL6</i> rearrangement by FISH or MYC overexpression by immunohistochemistry, Ki67 index ≥ 80% or nongerminal center immunophenotype, tumor measuring ≥5 cm and NCCN- IPI score ≥4. A total of 80 patients were treated with R-CHOP (<i>n</i> = 52, 65%) or DA.R-EPOCH (<i>n</i> = 28, 35%), with a median follow-up of 11.2 months (range: 0.7-151.3 months). The hazard ratios (HRs) for progression-free survival and overall survival were 0.79 [95% confidence interval (CI) 0.28%-2.29%, <i>p</i> = 0.67] and 0.86 (95% CI 0.26%-2.78%, <i>p</i> = 0.80), respectively for DA.R-EPOCH compared to R-CHOP. The total mean cost was USD106,940 ± USD39,351 and USD58,509 ± 24,588 for DA.R-EPOCH and R-CHOP respectively (<i>p</i> < 0.001). In our analysis, DA.R-EPOCH resulted comparable clinical outcomes and increased treatment-related expenses compared to R-CHOP in high-risk DLBCL.</p>","PeriodicalId":10368,"journal":{"name":"Clinical Hematology International","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/76/df/CHI-2-3-117.PMC8432333.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39476335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Haploidentical Hematopoietic Stem Cell Transplantation Followed by 'Post-Cyclophosphamide': The Future of Allogeneic Stem Cell Transplant.","authors":"Samuel Cytryn, Maher Abdul-Hay","doi":"10.2991/chi.d.200405.001","DOIUrl":"10.2991/chi.d.200405.001","url":null,"abstract":"<p><p>Allogeneic hematopoietic cell transplant (Allo-HCT) is a potentially curative therapy for many malignant and nonmalignant hematological diseases. However, a suitable human leukocyte antigens (HLAs)-matched donor may not be available when the patient is in urgent need of a stem cell transplant. This challenge has been ameliorated to a large extent by the introduction of haploidentical donors. This type of donor shares one HLA haplotype with the recipient. Therefore, a patient's full sibling has a 50% chance of being haploidentical and a patient's biologic parents and children will all be haploidentical, thus providing an immediately accessible, motivated donor for almost every recipient. Haploidentical transplants previously incurred prohibitively poor outcomes, preventing their widespread use. However, several recent advances have dramatically improved the results, making them a more viable donor source. In this review, we discuss different types of donors used for Allo-HCT with a particular focus on the use of haploidentical donors and their future potential.</p>","PeriodicalId":10368,"journal":{"name":"Clinical Hematology International","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/08/74/CHI-2-2-49.PMC8432344.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39477343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M Remberger, B Grønvold, M Ali, J Mattsson, T Egeland, K U Lundin, A Myhre, I Abrahamsen, D Heldal, I Dybedal, G E Tjønnfjord, T Gedde-Dahl, Y Fløisand
{"title":"The CD34<sup>+</sup> Cell Dose Matters in Hematopoietic Stem Cell Transplantation with Peripheral Blood Stem Cells from Sibling Donors.","authors":"M Remberger, B Grønvold, M Ali, J Mattsson, T Egeland, K U Lundin, A Myhre, I Abrahamsen, D Heldal, I Dybedal, G E Tjønnfjord, T Gedde-Dahl, Y Fløisand","doi":"10.2991/chi.d.200221.001","DOIUrl":"https://doi.org/10.2991/chi.d.200221.001","url":null,"abstract":"<p><p>The effect of CD34<sup>+</sup> cell dose in allogeneic hematopoietic stem cell transplantation (HSCT) on overall survival (OS) and incidence of acute and chronic graft-<i>versus</i>-host disease (GvHD) has not been established and few studies have been performed. Our single center analysis included 189 patients with hematological malignancies who received peripheral blood stem cell (PBSC) grafts from sibling donors. Myeloablative conditioning was used in 88 cases and 101 received reduced intensity conditioning. The median CD34<sup>+</sup> cell dose was 5.6 × 10<sup>6</sup>/kg (0.6-17.0). In the multivariate analysis, a CD34 cell dose of 6-7 × 10<sup>6</sup>/kg was associated with better OS and lower transplant-related mortality (TRM), while a dose of <5 × 10<sup>6</sup>/kg led to increased relapse and reduced chronic GVHD (cGVHD). A high CD34 cell-dose (>6.5 × 10<sup>6</sup>/kg) correlated with less acute GVHD (aGVHD) II-IV. We conclude that the CD34 cell dose has an impact on the outcome of HSCT from sibling donor PBSCs.</p>","PeriodicalId":10368,"journal":{"name":"Clinical Hematology International","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/87/3b/CHI-2-2-74.PMC8432346.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39477346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bogdan Popescu, Sheenu Sheela, Julie Thompson, Sophia Grasmeder, Therese Intrater, Christin B DeStefano, Christopher S Hourigan, Catherine Lai
{"title":"Timed sequential salvage chemotherapy for relapsed or refractory acute myeloid leukemia.","authors":"Bogdan Popescu, Sheenu Sheela, Julie Thompson, Sophia Grasmeder, Therese Intrater, Christin B DeStefano, Christopher S Hourigan, Catherine Lai","doi":"10.2991/chi.d.191128.001","DOIUrl":"10.2991/chi.d.191128.001","url":null,"abstract":"<p><p>Therapy for those with relapsed or refractory acute myeloid leukemia is suboptimal. Studies have suggested that timed sequential salvage combination cytotoxic chemotherapy may have particular utility for that indication. We report here a series of ten such adult patients treated sequentially at a single center with EMA (cytarabine 500 mg/m<sup>2</sup>/day as continuous infusion on days 1-3 and days 8-10, mitoxantrone 12 mg/m<sup>2</sup>/day on days 1-3, and etoposide 200 mg/m<sup>2</sup>/day as continuous infusion on days 8-10). The overall complete remission rate was 40% (including 3 of 4 of those with relapsed disease) but use of this regimen was associated with prolonged cytopenia and a high rate of infectious adverse events. Even with the availability of modern infectious prophylaxis and therapies, the EMA regimen is likely best reserved for those with relapsed disease treated with curative intent prior to an allogeneic hematopoietic cell transplant.</p>","PeriodicalId":10368,"journal":{"name":"Clinical Hematology International","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e4/8a/CHI-2-1-27.PMC7079712.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37752402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ehsan Shabbir, Umar Farooq, Burhan Yanes, Margarida Magalhaes-Silverman
{"title":"Repeat Endoscopy Affects Patient Management in Gastrointestinal Graft-<i>Versus</i>-Host Disease.","authors":"Ehsan Shabbir, Umar Farooq, Burhan Yanes, Margarida Magalhaes-Silverman","doi":"10.2991/chi.d.200220.001","DOIUrl":"https://doi.org/10.2991/chi.d.200220.001","url":null,"abstract":"<p><p>Graft <i>versus</i> host disease (GVHD) of the gut is associated with significant morbidity and mortality after allogeneic hematopoietic cell transplant (allo-HCT). No guidelines exist regarding repeat endoscopy after failure of first-line treatment with steroids. We aimed to study if repeat endoscopic biopsy can be helpful in these patients to guide treatment decisions. We retrospectively reviewed medical records of all patients who underwent repeat endoscopy for clinical suspicion of gastrointestinal (GI) GVHD after allo-HCT. Of the 318 patients, 24 underwent endoscopy twice after allo-HCT. At first endoscopy, 20 patients (80%) showed abnormal findings: 16 with GVHD alone, 1 with GVHD plus cytomegalovirus (CMV), and 3 with GVHD plus infectious colitis. On repeat endoscopy in these 20 patients with GVHD, 6 showed improvement leading to de-escalation of therapy, 8 showed worsening of GVHD including detection of CMV in 2 patients, and 2 had no histological changes. One patient with simultaneous GVHD and CMV diagnosed on first biopsy, displayed significant improvement leading to de-escalation of therapy. Three patients with GVHD along with infectious colitis on biopsy subsequently showed improvement on repeat biopsy leading to de-escalation of therapy. Among 4 patients with normal findings on first endoscopy, 3 had GVHD and 1 had epstein-barrvirus-associated post-transplant lymphoproliferative disorder (EBV-PTLD) on repeat procedures. This study supports the usefulness of repeat endoscopy in persistently symptomatic patients when there is no improvement after the initial treatment based on the results of the first endoscopy. Repeat endoscopy may guide therapy without significant complications.</p>","PeriodicalId":10368,"journal":{"name":"Clinical Hematology International","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c6/e1/CHI-2-2-69.PMC8432351.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39477344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}