Neil Dunavin

Mesenchymal Stromal Cells: What Is the Mechanism in Acute Graft-Versus-Host Disease?

After more than a decade of preclinical and clinical development, therapeutic infusion of mesenchymal stromal cells is now a leading investigational strategy for the treatment of acute graft-versus-host disease (GVHD). While their clinical use continues to expand, it is still unknown which of their immunomodulatory properties contributes most to their therapeutic activity. Herein we describe the proposed mechanisms, focusing on the inhibitory activity of mesenchymal stromal cells (MSCs) at immunologic checkpoints. A deeper understanding of the mechanism of action will allow us to design more effective treatment strategies.

Clinical comorbidity predictive measures in ex vivo T-cell-depleted allogeneic hematopoietic stem cell transplantation

Clinical comorbidity predictive measures in ex vivo T-cell-depleted allogeneic hematopoietic stem cell transplantation

Improved reproducibility and quality of GvHD biomarker assay: application of multiplex microfluidic channel system

Improved reproducibility and quality of GvHD biomarker assay: application of multiplex microfluidic channel system

Upregulation of chemokine CXCL10 enhances chronic pulmonary inflammation in tree shrew collagen-induced arthritis

Chronic pulmonary inflammation (CPI) gives rise to serious lung injuries in rheumatoid arthritis (RA) patients. However, the molecular mechanism underlying the pathogenesis of RA-associated CPI remains little understood. Here we established a novel tree shrew-based collagen-induced arthritis (TsCIA) model to study RA-associated CPI. Our results showed that typical CPI but not fibrosis developed pathologically in the TsCIA model. Furthermore, abnormal up-regulation of pulmonary chemokine CXCL10 was directly associated with lung damage. Specific blockage of CXCR3 (a CXCL10 receptor) significantly decreased the severity of CPI by decreasing the recruitment of inflammatory cells. Therefore, CXCL10 is proposed as a key player responsible for the development of TsCIA-associated CPI. Our findings also suggest that CXCR3 could be developed as a potential diagnosis biomarker for RA-associated CPI.

Outcomes of VDPACE with Immunomodulator Agent as a Salvage Therapy for Relapsed/Refractory Multiple Myeloma

27 mg/dL. Ibrutinib was held due to its common side effect, bleeding. The patient was referred to Urology to rule out bladder cancer with the concern of a prior history of cyclophosphamide treatment. Cystoscopy demonstrated mildly elevated bladder neck, otherwise normal for any acute pathology. Overall, it was thought that the benign bleeding could be from the prostatic urethra irritation and patient was started on tamsulosin. In the follow-up appointment patient had a bleeding for 20 minutes from the venipuncture site. The further evaluation for bleeding showed that patient had decreased vWF Ag (33%), vWF Activity (13%) and aVWFD was diagnosed. Meanwhile, patient’s IgM was 778 mg/dL. Ibrutinib was resumed considering that the IgM increased. In the next follow-up, patient’s bleeding symptoms were resolved and did not recur, his IgM decreased to 32 mg/dL and vWF Ag (229%), vWF Activity (204%) dramatically increased. Discussion: This case describes the challenge of diagnosing the etiology of bleeding in WM and highlights the importance of systematic approach. The incidence of hyperviscosity syndrome and related bleeding has decreased with early diagnosis of WM. Ibrutinib, a Bruton tyrosine kinase inhibitor used in WM has a main side effect of bleeding related to abnormalities in platelet aggregation. aVWFD can be associated with various mechanisms affecting vWF: autoantibodies, decreased synthesis, adsorption on cancer cells, damage. IgM autoantibodies against vWF in WM and associated aVWF disease is rarely observed. Although there are several mechanisms for bleeding in WM, the systematic approach to evaluate will be key to elucidate the underlying diverse mechanisms.

Mesenchymal stromal cell infusions for acute graft-versus-host disease: Rationale, data, and unanswered questions

Mesenchymal stem/stromal cells (MSCs) infusions are a promising investigational treatment strategy for steroid‐refractory acute graft‐versus‐host disease (GVHD). Herein we describe the rationale for their use in acute GVHD, the clinical data reported from animal and human studies to date, and we highlight recent areas of research and investigation that provide the basis for improvements in the next generation of studies.

Utility of Routine Surveillance Imaging for Hodgkin Disease following Autologous Transplant: Experiences from a Single Institution

Background: Surveillance scans performed after autologous stem cell transplant (auto-HCT) for patients with Hodgkin disease (HD) have no proven survival benefit. Methods: We studied survival differences among patients with HD after auto-HCT whose recurrences were detected on clinical history and exam, versus those detected on routine surveillance scan. Results: Among the 98 patients with HD that underwent auto-HCT from 2000 to 2014 at our institution, 30 relapsed, of which 21 were detected radiologically and 9 clinically. There were no statistically significant differences in patient characteristics between the 2 groups. The median time to progression was 118 days for the clinical cohort and 284 days for the radiological cohort (p = 0.05). Median overall survival (OS) was 728 days for the clinical cohort, and was not reached for the radiological cohort (p = 0.02). Discussion: In our review, most patients with HD after auto-HCT were diagnosed radiologically. Patients whose relapse was diagnosed clinically were likely to be detected earlier and have a shorter OS. Patients with aggressive disease may be detected when clinically relevant, regardless of scanning. Routine scanning may not be necessary in the majority of patients with HD following auto-HCT.

Utility of routine surveillance imaging for diffuse large B-cell lymphoma post autologous transplant: A single center experience

Surveillance scans after autologous stem cell transplant (auto-HCT) for patients with relapsed/refractory (RR) diffuse large B Cell lymphoma (DLBCL) have no proven survival benefit. We studied survival differences among patients with RR DLBCL post auto-HCT whose recurrences were detected clinically versus with routine surveillance imaging. Among the 139 patients with RR DLBCL that underwent auto-HCT from 2000 to 2014 at our institution, 37 relapsed: 21 clinical and 16 radiological. The median time to progression was 167u202fdays for the clinical cohort and 565u202fdays for the radiological cohort (pu202f=u202f0.03), and median overall survival (OS) was 587u202fdays and not reached, respectively (pu202f=u202f0.006). Most patients with relapsed DLBCL after auto-HCT were diagnosed clinically and were likely to be detected earlier and have a shorter OS. Relapse in patients with aggressive disease will likely be detected when clinically apparent, and the outcome of these patients is independent of the way the relapse is diagnosed. Thus, universal scanning after auto-HCT appears to have little benefit.