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Hand-foot syndrome and risk factors for occurrence in hematopoietic stem cell transplantation recipients
Kume, T., Shimizu, R., Akiyama, K., Tsuchiya, T., Shino, M., Ikeda, T., Iwai, S.
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 2022;30(2):1539-1546
Abstract
PURPOSE Hand-foot syndrome (HFS) is a typical skin disorder caused by the use of cytotoxic anticancer drugs and molecular targets. Similarly, various anticancer drugs have been used as a conditioning regimen for hematopoietic stem cell transplantation (HSCT), and skin disorders such as HFS have been reported. The aim of this study was to determine retrospectively the frequency of HFS in recipients who have received a first allogeneic HSCT and the risk factors for HFS occurrence. METHODS We retrospectively investigated the medical records of recipients who received their first allogeneic HSCT and neutrophil engraftment at Shizuoka Cancer Center from January 1, 2011, to December 31, 2019. RESULTS The occurrence of HFS was confirmed in 78 cases (48.1%), and no grade 3 HFS was confirmed. The median occurrence of HFS was 8 (- 3 to 19) days. In recipients with and without confirmed HFS, the median neutrophil engraftment day was 16.5 (10-33) and 15.0 (11-26) days, respectively (p = 0.013). Multivariate analysis indicated that the frequency of HFS was statistically significantly higher in women (p = 0.032), recipients administered busulfan (Bu) four times daily (p = 0.011), and recipients previously treated with anthracycline (p = 0.002). CONCLUSION Attention should be paid to HFS that occurs due to the conditioning regimen for HSCT in women, recipients who received 0.8 mg/kg of Bu four times a day, and recipients with a history of anthracycline administration, as HFS may affect the duration to neutrophil engraftment.
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Dermatology Impact on the Care of Children with Chronic Graft-versus-Host Disease of the Skin
Garza-Mayers, A. C., Anderson, L. E., Yu, J., Huang, J. T.
Journal of the American Academy of Dermatology. 2019
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Donor skin allograft survival after bone marrow transplantation: Case report and systematic review of the literature☆
Nunez-Villaveiran, T., Feasel, P., Keenan, S., Aliotta, R., Bosler, D., Stearns, D., Bergfeld, W., Gurunluoglu, R.
Journal of Plastic, Reconstructive & Aesthetic Surgery : Jpras. 2019;72(1):23-34
Abstract
BACKGROUND We present a case of skin allograft survival in a patient who previously received a bone marrow transplant from the same HLA-matched donor. DNA fingerprinting of skin biopsies showed mixed cellularity originating from the donor and recipient (68% and 32% donor DNA in the allograft skin and the native recipient's skin, respectively). Histologic sections demonstrated both grade 3/4 rejection and graft-versus-host-disease. We have conducted a systematic review in search for other cases of donor skin allograft survival after a bone marrow or hematopoietic stem cell transplantation. METHODS All reported cases in English, Spanish, French, and German were captured using the electronic databases. Bibliographies of relevant articles were manually searched. RESULTS Nineteen patients (12 females) who received skin allografts from their bone marrow or hematopoietic stem cell donors were identified. Average age was 27.2 years (range: 5 months to 64 years). Skin allografts were used to treat graft-versus-host-disease, Herlitz junctional epidermolysis bullosa, and to test tolerance before a kidney transplantation from the same donor. Eight cases were not receiving immunosuppressive therapy. Allografts survived in all patients. In three patients, skin punch biopsies were taken, and these biopsies demonstrated mixed donor and recipient cellularity. The pathology result is specified in two more cases, with no signs of rejection. CONCLUSIONS The same donor skin allografts may be a safe option to treat severe cutaneous conditions in recipients of a bone marrow/hematopoietic stem cell transplantation. However, future studies are needed to confirm these results.
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The Anatomic Distribution of Skin Involvement in Patients with Incident Chronic Graft-versus-Host Disease
Gandelman, J. S., Zic, J., Dewan, A. K., Lee, S. J., Flowers, M., Cutler, C., Pidala, J., Chen, H., Jagasia, M. H., Tkaczyk, E. R.
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2018
Abstract
Little is known about the anatomic distribution of cutaneous chronic graft-versus-host disease (cGVHD). Using data from the cGVHD Consortium Improving Outcomes Assessment Study, we describe the frequency and extent of erythema, superficial, and deep sclerosis in 8 anatomic sites in patients with incident disease (new cGVHD diagnosis within three months of study entry) and on systemic therapy. Of 339 patients with incident disease, 182 (54%) had skin involvement. When an extremity was involved, the same type of disease was present contralaterally in 92% of cases, revealing a high level of symmetry. As anticipated, erythema was the most common incident feature; however, sclerotic skin involvement at time of cGVHD diagnosis was more common than suggested by prior studies. Erythema occurred in 155 (85%) and sclerosis in 53 (29%) of the patients with skin involvement (respectively 46% and 16% of the the entire cohort of 339 incident cGVHD cases). Erythema was least common on the lower extremities (n=71, 39% of patients with skin involvement). Moveable sclerosis was rare on the head, neck, and scalp (n=4, 2%). Deep sclerosis did not occur in this region, and instead was most likely on the upper (n=14, 8%) and lower extremities (n=14, 8%). More than half of patients with erythema (n=107, 58.7%) had diffuse involvement (4 or more of 8 sites involved), compared to less than a third of those with sclerosis (n=16, 30.2%).
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Longstanding alopecia and nail dystrophy are associated with more severe overall chronic graft-versus-host disease in adults
Naftulin, J. S., Penzi, L. R., Manatis-Lornell, A., Yasuda, M. R., Porter, M. L., Saavedra, A., Senna, M. M.
Bone marrow transplantation. 2018
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6.
Role of graft-versus-host disease in the development of secondary skin cancers in hematopoietic stem cell transplant recipients: A meta-analysis
Rambhia, P. H., Conic, R. Z., Atanaskova-Mesinkovska, N., Piliang, M., Bergfeld, W. F.
Journal of the American Academy of Dermatology. 2018;79(2):378-380.e3
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Clinical Commentary
What is known?
NIHMS979097
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7.
Tissue Damage Caused by Myeloablative, but Not Non-Myeloablative, Conditioning before Allogeneic Stem Cell Transplantation Results in Dermal Macrophage Recruitment without Active T-Cell Interaction
van Balen, P., van der Zouwen, B., Kruisselbrink, A. B., Eefting, M., Szuhai, K., Jordanova, E. S., Falkenburg, J. H. F., Jedema, I.
Frontiers in immunology. 2018;9:331
Abstract
Introduction: Conditioning regimens preceding allogeneic stem cell transplantation (alloSCT) can cause tissue damage and acceleration of the development of graft-versus-host disease (GVHD). T-cell-depleted alloSCT with postponed donor lymphocyte infusion (DLI) may reduce GVHD, because tissue injury can be restored at the time of DLI. In this study, we investigated the presence of tissue injury and inflammation in skin during the period of hematologic recovery and immune reconstitution after alloSCT. Methods: Skin biopsies were immunohistochemically stained for HLA class II, CD1a, CD11c, CD40, CD54, CD68, CD86, CD206, CD3, and CD8. HLA class II-expressing cells were characterized as activated T-cells, antigen-presenting cells (APCs), or tissue repairing macrophages. In sex-mismatched patient and donor couples, origin of cells was determined by multiplex analysis combining XY-FISH and fluorescent immunohistochemistry. Results: No inflammatory environment due to pretransplant conditioning was detected at the time of alloSCT, irrespective of the conditioning regimen. An increase in HLA class II-positive macrophages and CD3 T-cells was observed 12-24 weeks after myeloablative alloSCT, but these macrophages did not show signs of interaction with the co-localized T-cells. In contrast, during GVHD, an increase in HLA class II-expressing cells coinciding with T-cell interaction was observed, resulting in an overt inflammatory reaction with the presence of activated APC, activated donor T-cells, and localized upregulation of HLA class II expression on epidermal cells. In the absence of GVHD, patient derived macrophages were gradually replaced by donor-derived macrophages although patient-derived macrophages were detectable even 24 weeks after alloSCT. Conclusion: Conditioning regimens cause tissue damage in the skin, but this does not result in a local increase of activated APC. In contrast to the inflamed situation in GVHD, when interaction takes place between activated APC and donor T-cells, the tissue damage caused by myeloablative alloSCT results in dermal recruitment of HLA class II-positive tissue repairing macrophages co-existing with increased numbers of patient- and donor-derived T-cells, but without signs of specific interaction and initiation of an immune response. Thus, the local skin damage caused by the conditioning regimen appears to be insufficient as single factor to provoke GVHD induction.
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Non-malignant late cutaneous changes after allogeneic hematopoietic stem cell transplant in children
Huang, J. T., Song, J. S., Hawryluk, E. B., London, W. B., Guo, D., Sridharan, M., Fisher, D. E., Lehmann, L. E., Duncan, C. N.
Journal of the American Academy of Dermatology. 2018
Abstract
BACKGROUND There are limited pediatric data on non-malignant cutaneous changes, including autoimmune conditions and permanent alopecia, after hematopoietic stem cell transplantation (HSCT). OBJECTIVE We sought to characterize late cutaneous changes and associated risk factors after allogeneic HSCT in children. METHODS A cross-sectional cohort study of pediatric HSCT recipients was performed at a single institution. All participants underwent a full skin examination. RESULTS Median visit age was 13.8 years with median time post-HSCT of 3.6 years. Of 85 patients, 14% (n=12) had vitiligo, 16% (n=14) had psoriasis/sebopsoriasis, 25% (n=21) had alopecia, and 6% (n=5) had nail changes. Factors significantly associated with vitiligo included a history of chronic graft-versus-host disease (cGVHD), transplant indication of primary immunodeficiency, and younger age at transplant (<10 years of age). Fifty-two percent of patients with alopecia had androgenetic alopecia patterns. Factors significantly associated with alopecia included cGVHD, busulfan conditioning, and family history of early male pattern alopecia. All patients with nail changes had cGVHD. LIMITATIONS The cross-sectional design did not allow time of onset identification. Histopathologic correlation was not performed. CONCLUSION Pediatric HSCT recipients, particularly those with cGVHD, are at risk for developing non-malignant late cutaneous changes.
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Prevalence of cutaneous viral infections in incident cutaneous squamous cell carcinoma detected among chronic lymphocytic leukemia and hematopoietic stem cell transplant patients
Hampras, S. S., Locke, F. L., Chavez, J. C., Patel, N. S., Giuliano, A. R., Miller, K., Gheit, T., Tommasino, M., Rollison, D. E.
Leukemia & lymphoma. 2018;59(4):911-917
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Abstract
The role of cutaneous viral infections in the development of non-melanoma skin cancer (NMSC), including cutaneous squamous cell carcinoma (SCC), among chronic lymphocytic leukemia (CLL) and blood and marrow transplant (BMT) patients is not established. CLL (n = 977) and BMT (n = 3587) patients treated at the Moffitt Cancer Center were included in a retrospective cohort study. Human papillomavirus (HPV) and human polyomavirus (HPyV) DNA were examined in a subset of incident SCC tumors. Five-year cumulative incidence of NMSC was 1.42% in both BMT (n = 31 NMSCs) and CLL (n = 18 NMSCs) cohorts. Of the nine SCC tumors examined from each cohort, 22.2% and 33.3% were positive for viral DNA in the transplant (HPV 65, MCV) and CLL (HPV 38, HPV 15, HPyV6) cohort, respectively. Enhanced skin cancer screening of BMT/CLL patients should be conducted to better capture incident NMSCs and examine the role of viral infections in these tumors.
Clinical Commentary
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What is known?
NIHMS1504705
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10.
Risk of melanocytic nevi and nonmelanoma skin cancer in children after allogeneic hematopoietic stem cell transplantation
Song, J. S., London, W. B., Hawryluk, E. B., Guo, D., Sridharan, M., Fisher, D. E., Lehmann, L. E., Duncan, C. N., Huang, J. T.
Bone Marrow Transplantation. 2017;52(7):989-997
Abstract
There is a known increased risk of skin cancer in the adult population after hematopoietic stem cell transplantation (HSCT). However, late dermatologic effects that children may experience after HSCT have not been well described. The primary objective of this study was to characterize nevi and skin cancers affecting children after allogeneic HSCT. A cross-sectional cohort study of 85 pediatric HSCT recipients and 85 controls matched for age, sex and skin phototype was performed at a single institution. All participants underwent a full skin examination. Median age at study visit was 13.8 years in HSCT patients with median time post-HSCT of 3.6 years. HSCT patients had significantly more nevi than control patients (median (range): 44 (0-150) vs 11 (0-94), P<0.0001). HSCT patients also had significantly more nevi >5mm in diameter and atypical nevi than controls. Factors associated with increased nevus count included malignant indication for HSCT, pretransplant chemotherapy, TBI exposure and myeloablative conditioning. A total of 16.5% of HSCT patients developed cancerous, precancerous lesions and/or lentigines. Our study suggests that pediatric HSCT recipients have an increased risk of benign and atypical melanocytic proliferations and nonmelanoma skin cancer that can manifest even during childhood.