Complications of Allogeneic Hematopoietic Stem Cell Transplantation

Arnaout, Karim; Patel, Nisarg; Jain, Maneesh; El-Amm, Joelle; Amro, Farah H.; Tabbara, Imad A.

doi:10.3109/07357907.2014.919301

Cited by 72 publications

(48 citation statements)

References 139 publications

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“…The development of supportive cares for many complications like infectious diseases and graft versus host disease (GVHD) has remarkably improved the outcomes of allo-HSCT [1]. However, severe acute GVHD that occurres within the first 100 days after allo-HSCT is one of the most critical problems.…”

Section: Introductionmentioning

confidence: 99%

Human Mesenchymal Stem Cell Therapy for Acute Graft Versus Host Disease

Yoshioka¹,

Miura²

2016

Transl Med

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Acute graft versus host disease (GVHD) is the most critical complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The understanding of major histocompatibility complex (MHC) and the development of acute GVHD prophylaxis have contributed to decreasing the incidence of severe acute GVHD. However, these progresses expand the chance of receiving allo-HSCT from human leukocyte antigen (HLA) mismatched donor. In addition, the expanding of indication for allo-HSCT to elderly patients or patients with organ dysfunction by the pervasiveness of reduced-intensity conditioning is associated with increased risk of acute GVHD. Unexpectedly, severe refractory acute GVHD can occur even in allo-HSCT from HLA matched sibling donor. The first line therapy for severe acute GVHD is corticosteroid, but the second line therapy has not been established and the prognosis of steroid-resistant acute GVHD remains poor. Recently, the efficacy of human bone marrow mesenchymal stem cell (MSC) therapy for steroid-resistant acute GVHD has been consistently reported. MSCs are approved as a cell therapy drug for steroid-resistant acute GVHD in some countries. We here review the history and the future of MSC therapy for acute GVHD.

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Section: Introductionmentioning

confidence: 99%

Human Mesenchymal Stem Cell Therapy for Acute Graft Versus Host Disease

Yoshioka¹,

Miura²

2016

Transl Med

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“…cGVHD has been associated with a reduced risk of relapse, possibly because of a concomitant graft-versus-leukemia effect [4][5][6]. Despite this, cGVHD correlates with increased morbidity and mortality and has a major impact on the quality of life of subjects who have undergone allo-HSCT [7].…”

Section: Introductionmentioning

confidence: 99%

A Single-Center Pilot Prospective Study of Topical Application of Platelet-Derived Eye Drops for Patients with Ocular Chronic Graft-versus-Host Disease

Zallio

Mazzucco

Monaco

et al. 2016

Biology of Blood and Marrow Transplantation

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a b s t r a c tOcular involvement of chronic graft-versus-host disease (cGVHD) is a complication that occurs in up to 60% of patients after allogeneic hematopoietic stem cell transplantation. Conventional therapeutic options include medical and surgical procedures that are administered depending on the severity of the condition, but most of them have provided unsatisfactory results and, to date, there is no consensus about treatment. We considered that topical application of a platelet lysate, administered as eye drops, might be considered an alternative worthwhile of investigation to treat ocular surface disorders in patients suffering from cGVHD. Therefore, we conducted a single-center prospective pilot study to assess the efficacy and safety of using eye drops made from reconstituted lysed platelet concentrate. Twenty-six patients with ocular cGVHD were eligible for the study; all but 2 completed their scheduled 1-year treatment and complied with the hematologic and ophthalmic regimen. At their first assessment interviews, after 30 days of treatment, 91% of patients reported an improvement in their symptoms and for 32%, substantive objective differences were measured. Remission of corneal damage was seen for 86% of our cohort, and improved National Institutes of Health scores for 73%, of whom 8% achieved the best score of 0 (ie, nonedry eye). Similar results were seen at later time points. Comparing outcomes for our patient cohort to those determined retrospectively for patients in our institutional database revealed a 5-year overall survival (OS) of 65%. This OS is comparable to patients with limited cGVHD (75%) and is superior to that of patients with nonocular extensive cGVHD or without cGVHD (30% and 59%, respectively) (P ¼ .013). Our results suggest that platelet-derived eye drops are a safe, practical, and well-tolerated therapeutic option that offers substantial benefits for most patients affected by ocular cGVHD at onset. The favorable OS of our patient cohort suggests that this topical therapy, rather than systemic immunosuppression, may be the treatment of choice. Ó

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“…In the early post--HSCT period (<100 days), complications that commonly arise include infection, acute GvHD (aGvHD), and sinusoidal obstructive syndrome (SOS) [28]. Bacterial, fungal and viral infection contribute significantly to morbidity and mortality as patients are typically immunocompromised following conditioning [29].…”

Section: Potential Complications In the Post--transplantation Periodmentioning

confidence: 99%

“…Graft failure is another complication that occurs in ~5% of cases and can be associated with host--mediated immunological rejection, reduced intensity conditioning regimens, infection, abnormal marrow microenvironment, and transplantation of a graft with low cell numbers [34]. Graft failure is managed with the administration of haematopoietic growth factors and/or a second graft transplant that may require pre--conditioning [28].…”

Section: Potential Complications In the Post--transplantation Periodmentioning

confidence: 99%

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Device and application development for haematopoietic stem and progenitor cell (HSPC) and mesenchymal stromal cell (MSC) 3D spheroid cultures

Futrega¹

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KeywordsAIM 2: Utilization of the high throughput microwell platform to manufacture HSPC/MSC spheroids to improve the efficacy of direct BM transplantation.AIM 3: Development of an improved microwell platform that retains spheroids within discrete microwells throughout culture. AIM 4:Characterization of HSPC surface marker change in response to microwell material. DEVICE AND APPLICATION DEVELOPMENT FOR HSPC AND MSC 3D SPHEROID CULTURES iiiChapter 2 describes the development of a high throughput HSPC/MSC 3D spheroid co--culture embodied in AIM 1. I developed a high throughput polydimethylsiloxane (PDMS) microwell platform that enabled the manufacture of thousands of uniform 3D multicellular co--culture spheroids. Spheroids were assembled such that each contained 25--to--400 BM--derived MSC and 10 CB--derived CD34 + cells (a cell population enriched for HSPC). The outcomes from this Chapter guided the design of the subsequent three chapters. The specific outcomes and subsequent study results were as follows:Chapter 3: As described in Chapter 2, only modest improvements in expansion could be achieved by co--culturing HSPC in 3D MSC spheroids using a microwell platform. We reasoned that the 3D spheroids could, however, function as a biologically active anchor to improve direct BM transplantation outcomes. In this Chapter, we contrasted transplantation methods, including the use of MSC suspensions and 3D multicellular spheroids to modulate human CB--derived CD34 + cell retention within the BM cavity of NOD/SCID gamma (NSG) mice. Analysis revealed that the BM of injected femurs in some animals was saturated with human cells, while distal haematopoietic tissue engraftment was poor. These data show, for the first time, that retention of human haematopoietic cells within the BM enhances local engraftment at the expense of systemic engraftment.Chapter 4: As identified in Chapter 2, improvements in 3D spheroid co--cultures will require that the microwell platform is compatible with repeated medium exchange or dilution feeding. Multiple partial or complete medium exchanges can displace spheroids from discrete microwells, and this can result in either the loss of spheroids from culture, or spheroid amalgamation when displaced microtissues fall into common microwells. In this Chapter, I describe the first microwell platform that incorporates a mesh to retain microtissues within discrete microwells. We called this platform the microwell--mesh. We show that bonding a nylon mesh with an appropriate pore size over the microwell openings allows single cells to pass through the mesh into the microwells during the seeding process, but subsequently retains assembled microtissues within discrete microwells.Chapter 5: As identified in Chapter 2, the presence of PDMS, the material used to fabricate the microwell platform, altered CD38 surface expression on CB--derived CD34 + cells. Previous reports have shown that inhibition of retinoic acid signaling down--regulated CD38 iv DEVICE AND APPLICATION DEVELOPMENT FOR HSPC AND MSC 3D SPHE...

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Complications of Allogeneic Hematopoietic Stem Cell Transplantation

Cited by 72 publications

References 139 publications

Human Mesenchymal Stem Cell Therapy for Acute Graft Versus Host Disease

Human Mesenchymal Stem Cell Therapy for Acute Graft Versus Host Disease

A Single-Center Pilot Prospective Study of Topical Application of Platelet-Derived Eye Drops for Patients with Ocular Chronic Graft-versus-Host Disease

Device and application development for haematopoietic stem and progenitor cell (HSPC) and mesenchymal stromal cell (MSC) 3D spheroid cultures

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