Hematopoietic Cell Transplantation for Systemic Sclerosis—A Review
Abstract
:1. Introduction
2. Proposed Mechanisms of Action of Autohct on SSc
2.1. Partial Lymphoablation Followed by the Crowding out of the Persisting Autoreactive T Cells by De Novo Generated T Cells
2.2. Partial Lymphoablation Followed by the Functional Tolerization of Autoreactive T Cells
2.3. Fast Reconstitution of Tregs
2.4. Less Proinflammatory/More Anti-Inflammatory Myeloid Cells?
2.5. Role of B Cell?
2.6. Non-Immunologic Mechanisms?
3. Clinical Results
4. Patient Selection
5. Transplant Protocols
5.1. Mobilization
5.2. Graft Manipulation/CD34 Cell Selection
5.3. Conditioning
5.4. Supportive Care
6. Complications of HCT
6.1. Acute Complications
6.2. Long-Term Complications
6.2.1. Infertility/Premature Menopause
6.2.2. Malignancy
6.2.3. New Autoimmune Disease
7. Relapse/SSc Progression
7.1. Definition
7.2. Frequency of Relapse
7.3. Treatment of Relapse
8. Allogeneic HCT
9. Future Works
9.1. HCT as First vs. Next Line Treatment?
9.2. Refining Patient Selection
9.3. Comparison of VARIABLES in HCT Techniques and Development of New HCT Techniques
9.4. Role of Maintenance Therapy
9.5. Cellular Therapies Other Than AutoHCT
10. Summary
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Manifestation/Aspect of SSc | Effect of HCT | Level of Evidence ** | ||
---|---|---|---|---|
Mortality | Improvement | High [21,22,23] | ||
Quality of life | Improvement | High [21,22,23,65,71,72,73] | ||
Skin tightness (mRSS) [74] | Improvement | High [21,22,23,24,25,44,65,66,72,75,76,77,78,79] | ||
Pain [80,81,82] | Improvement | Medium [71] | ||
Lung function (FVC) [83,84] | Mild improvement | High [21,22,23,28,75,78,85,86,87] | ||
Interstitial lung disease (CT) [88] | Improvement of inflammation, probably not fibrosis | Medium [28,85,86,87,89,90,91] | ||
Pulmonary arterial hypertension | Preventing PAH; effect on established PAH is unknown | High [23] | ||
Heart failure [92,93,94] | Preventing or delaying HF; effect on established HF is unknown | High [23,95] | ||
Esophageal volume/dilation (CT) | Worsening | Medium [96] | ||
Esophageal motility | Stabilization or mild improvement(?) if pre-transplant hypomotility; no improvement if pre-transplant amotility | Medium, but unpublished [M.W. et al., publication in progress] | ||
Gastrointestinal symptoms [97] | Improvement | Medium [71] | ||
Renal function [98] | Worsening | High, but shown in only 1 of 3 randomized studies [22] | ||
Range of motion of joints | Improvement | Medium [77] | ||
Hand grip strength | Improvement | Medium [77] | ||
Exercise capacity | Improvement | Medium [99] | ||
Myositis | May improve | Low [100] | ||
Peripheral neuropathy | May improve | Low [101] | ||
Nailfold capillaries [102] | May improve | Medium [103] | ||
Capillary density on skin biopsy | No improvement | Medium [104] | ||
Raynaud’s phenomenon | May improve late after HCT | Medium [71] | ||
Calcinosis | May improve | Low [105] |
Conventional Criteria | Expanded Criteria | |
---|---|---|
Age | 18–65 Years of Age | No Expansion |
Disease Duration | ≤5 years from first non-Raynaud’s manifestation | Shah et al. 2021 [109]:
|
SSc Subtype/mRSS | dcSSc
| Burt et al. 2021:
|
Smoking | Non-current smokers | No expansion |
Pregnancy | Non-pregnant individuals | No expansion |
Cardiopulmonary Involvement |
| Shah et al. 2021:
|
Hepatic Involvement | No evidence of persistent or progressive hepatic impairment defined as persistent increase in rate or twice-normal transaminases/bilirubin | No expansion |
Renal Involvement | GFR > 40 mL/min | No expansion |
Hematolymphatic System Status | No evidence of persistent neutropenia (neutrophils <0.5 × 109/L), thrombocytopenia (<50 × 109/L), or CD4 lymphopenia (<200/mm3) | No expansion |
Nutritional Status | BMI ≥ 18 kg/m2, Albumin ≥ 20 mg/L | No expansion |
Other | No active neoplasia or concomitant myelodysplasia, no acute or chronic uncontrolled infection, good patient compliance | No expansion |
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Levin, D.; Osman, M.S.; Durand, C.; Kim, H.; Hemmati, I.; Jamani, K.; Howlett, J.G.; Johannson, K.A.; Weatherald, J.; Woo, M.; et al. Hematopoietic Cell Transplantation for Systemic Sclerosis—A Review. Cells 2022, 11, 3912. https://doi.org/10.3390/cells11233912
Levin D, Osman MS, Durand C, Kim H, Hemmati I, Jamani K, Howlett JG, Johannson KA, Weatherald J, Woo M, et al. Hematopoietic Cell Transplantation for Systemic Sclerosis—A Review. Cells. 2022; 11(23):3912. https://doi.org/10.3390/cells11233912
Chicago/Turabian StyleLevin, Daniel, Mohammed S. Osman, Caylib Durand, Hyein Kim, Iman Hemmati, Kareem Jamani, Jonathan G. Howlett, Kerri A. Johannson, Jason Weatherald, Matthew Woo, and et al. 2022. "Hematopoietic Cell Transplantation for Systemic Sclerosis—A Review" Cells 11, no. 23: 3912. https://doi.org/10.3390/cells11233912