-
Journal of the American Academy of... Dec 2021Patients with cutaneous T-cell lymphoma (CTCL) are at a higher risk of developing second malignancies. However, rates of incidence vary significantly across studies. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patients with cutaneous T-cell lymphoma (CTCL) are at a higher risk of developing second malignancies. However, rates of incidence vary significantly across studies.
METHODS
A systematic review and meta-analysis of articles published between 1950 and 2019 was performed to evaluate the risk of second malignancies in patients with CTCL.
RESULTS
We identified 10 eligible studies, including 12 patient cohorts, with 5.9% to 16.8% of patients developing second malignancies. All studies showed a male predominance for patients developing second malignancies. The mean age across the studies ranged from 44.6 to 68.0 years. The time between the diagnosis of CTCL and second malignancy ranged from 2.1 to 5.4 years (mean, 3.29 y; 95% confidence interval [CI], 2.69-5.15). Meta-analysis showed a standardized incidence ratio of 2.18 (95% CI, 1.43-2.93) for all malignancies. The standardized incidence ratios were 15.25 (95% CI, 7.70-22.79) for Hodgkin lymphoma, 4.96 (95% CI, 3.58-6.33) for non-Hodgkin lymphoma, 1.69 (95% CI, 1.18-2.21) for lung cancer, 1.72 (95% CI, 1.18-2.21) for bladder cancer, and 3.09 (95% CI, 1.77-6.43) for melanoma.
CONCLUSIONS
We find that patients with CTCL are at increased risk of second malignancies, especially Hodgkin and non-Hodgkin lymphoma, lung cancer, bladder cancer, and melanoma. These findings provide evidence of a population at increased risk of malignancy. Early detection may decrease the morbidity burden of second malignancies, thus providing a strong rationale for prospective screening studies.
Topics: Adult; Aged; Humans; Lung Neoplasms; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell, Cutaneous; Male; Melanoma; Middle Aged; Mycosis Fungoides; Neoplasms, Second Primary; Prospective Studies; Skin Neoplasms; Urinary Bladder Neoplasms
PubMed: 32822803
DOI: 10.1016/j.jaad.2020.06.1033 -
The Cochrane Database of Systematic... Jul 2020Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma, a malignant, chronic disease initially affecting the skin. Several therapies are available,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma, a malignant, chronic disease initially affecting the skin. Several therapies are available, which may induce clinical remission for a time. This is an update of a Cochrane Review first published in 2012: we wanted to assess new trials, some of which investigated new interventions.
OBJECTIVES
To assess the effects of interventions for MF in all stages of the disease.
SEARCH METHODS
We updated our searches of the following databases to May 2019: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We searched 2 trials registries for additional references. For adverse event outcomes, we undertook separate searches in MEDLINE in April, July and November 2017.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of local or systemic interventions for MF in adults with any stage of the disease compared with either another local or systemic intervention or with placebo.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. The primary outcomes were improvement in health-related quality of life as defined by participants, and common adverse effects of the treatments. Key secondary outcomes were complete response (CR), defined as complete disappearance of all clinical evidence of disease, and objective response rate (ORR), defined as proportion of patients with a partial or complete response. We used GRADE to assess the certainty of evidence and considered comparisons of psoralen plus ultraviolet A (PUVA) light treatment as most important because this is first-line treatment for MF in most guidelines.
MAIN RESULTS
This review includes 20 RCTs (1369 participants) covering a wide range of interventions. The following were assessed as either treatments or comparators: imiquimod, peldesine, hypericin, mechlorethamine, nitrogen mustard and intralesional injections of interferon-α (IFN-α) (topical applications); PUVA, extracorporeal photopheresis (ECP: photochemotherapy), and visible light (light applications); acitretin, bexarotene, lenalidomide, methotrexate and vorinostat (oral agents); brentuximab vedotin; denileukin diftitox; mogamulizumab; chemotherapy with cyclophosphamide, doxorubicin, etoposide, and vincristine; a combination of chemotherapy with electron beam radiation; subcutaneous injection of IFN-α; and intramuscular injections of active transfer factor (parenteral systemics). Thirteen trials used an active comparator, five were placebo-controlled, and two compared an active operator to observation only. In 14 trials, participants had MF in clinical stages IA to IIB. All participants were treated in secondary and tertiary care settings, mainly in Europe, North America or Australia. Trials recruited both men and women, with more male participants overall. Trial duration varied from four weeks to 12 months, with one longer-term study lasting more than six years. We judged 16 trials as at high risk of bias in at least one domain, most commonly performance bias (blinding of participants and investigators), attrition bias and reporting bias. None of our key comparisons measured quality of life, and the two studies that did presented no usable data. Eighteen studies reported common adverse effects of the treatments. Adverse effects ranged from mild symptoms to lethal complications depending upon the treatment type. More aggressive treatments like systemic chemotherapy generally resulted in more severe adverse effects. In the included studies, CR rates ranged from 0% to 83% (median 31%), and ORR ranged from 0% to 88% (median 47%). Five trials assessed PUVA treatment, alone or combined, summarised below. There may be little to no difference between intralesional IFN-α and PUVA compared with PUVA alone for 24 to 52 weeks in CR (risk ratio (RR) 1.07, 95% confidence interval (CI) 0.87 to 1.31; 2 trials; 122 participants; low-certainty evidence). Common adverse events and ORR were not measured. One small cross-over trial found once-monthly ECP for six months may be less effective than twice-weekly PUVA for three months, reporting CR in two of eight participants and ORR in six of eight participants after PUVA, compared with no CR or ORR after ECP (very low-certainty evidence). Some participants reported mild nausea after PUVA but no numerical data were given. One participant in the ECP group withdrew due to hypotension. However, we are unsure of the results due to very low-certainty evidence. One trial comparing bexarotene plus PUVA versus PUVA alone for up to 16 weeks reported one case of photosensitivity in the bexarotene plus PUVA group compared to none in the PUVA-alone group (87 participants; low-certainty evidence). There may be little to no difference between bexarotene plus PUVA and PUVA alone in CR (RR 1.41, 95% CI 0.71 to 2.80) and ORR (RR 0.94, 95% CI 0.61 to 1.44) (93 participants; low-certainty evidence). One trial comparing subcutaneous IFN-α injections combined with either acitretin or PUVA for up to 48 weeks or until CR indicated there may be little to no difference in the common IFN-α adverse effect of flu-like symptoms (RR 1.32, 95% CI 0.92 to 1.88; 82 participants). There may be lower CR with IFN-α and acitretin compared with IFN-α and PUVA (RR 0.54, 95% CI 0.35 to 0.84; 82 participants) (both outcomes: low-certainty evidence). This trial did not measure ORR. One trial comparing PUVA maintenance treatment to no maintenance treatment, in participants who had already had CR, did report common adverse effects. However, the distribution was not evaluable. CR and OR were not assessable. The range of treatment options meant that rare adverse effects consequently occurred in a variety of organs.
AUTHORS' CONCLUSIONS
There is a lack of high-certainty evidence to support decision making in the treatment of MF. Because of substantial heterogeneity in design, missing data, small sample sizes, and low methodological quality, the comparative safety and efficacy of these interventions cannot be reliably established on the basis of the included RCTs. PUVA is commonly recommended as first-line treatment for MF, and we did not find evidence to challenge this recommendation. There was an absence of evidence to support the use of intralesional IFN-α or bexarotene in people receiving PUVA and an absence of evidence to support the use of acitretin or ECP for treating MF. Future trials should compare the safety and efficacy of treatments to PUVA, as the current standard of care, and should measure quality of life and common adverse effects.
Topics: Acitretin; Antineoplastic Agents; Bexarotene; Combined Modality Therapy; Humans; Immunologic Factors; Interferon-alpha; Mycosis Fungoides; Neoplasm Staging; PUVA Therapy; Photochemotherapy; Photopheresis; Randomized Controlled Trials as Topic; Skin Neoplasms
PubMed: 32632956
DOI: 10.1002/14651858.CD008946.pub3 -
Journal of Cutaneous Pathology Mar 2020Reflectance confocal microscopy (RCM) is a non-invasive imaging technique that provides dynamic information and allows in vivo monitoring, with excellent histologic...
BACKGROUND
Reflectance confocal microscopy (RCM) is a non-invasive imaging technique that provides dynamic information and allows in vivo monitoring, with excellent histologic correlation. In the last decade, the use of RCM for cutaneous T-cell lymphomas (CTCL) has been reported. CTCL may require multiple biopsies for diagnosis due to its equivocal clinical presentation. RCM was described as a possible tool to help determine the best site for skin biopsy. This study aims to systematically review all RCM features reported in literature for CTCL.
METHOD
A systematic literature search concerning CTCL evaluated by RCM was performed in eight electronic databases until May 2019 following PRISMA-DTA quality assessment.
RESULTS
Eighteen RCM features were described in patients with CTCL. The most frequent were: interface dermatitis (89%), epidermal lymphocytes (82%), epidermal architectural disarray (81%), and vesicle-like structure (Pautrier microabscess) (51%).
CONCLUSION
In order to establish comparable parameters among the studies identified, we proposed descriptors for CTCL features and a grading system to quantify them. This will facilitate to define the role of RCM in the diagnosis and monitoring of CTCL patients.
Topics: Dermoscopy; Humans; Lymphoma, T-Cell, Cutaneous; Microscopy, Confocal
PubMed: 31618473
DOI: 10.1111/cup.13598 -
Biology of Blood and Marrow... Jan 2020Mycosis fungoides and Sézary syndrome are the most common types of primary cutaneous T cell lymphomas. The clinical presentation of mycosis fungoides is generally... (Meta-Analysis)
Meta-Analysis
Mycosis fungoides and Sézary syndrome are the most common types of primary cutaneous T cell lymphomas. The clinical presentation of mycosis fungoides is generally indolent, whereas Sézary syndrome represents a more aggressive disease variant. Stage at diagnosis is the most important determinant of long-term survival outcome. Although most patients present with early-stage disease, those who develop progressive disease or have an advanced stage represent a therapeutic challenge because of a lack of effective therapies. Allogeneic hematopoietic cell transplantation (allo-HCT) has been used as a potentially curative treatment modality with encouraging long-term outcomes. However, a lack of randomized controlled data remains, and the published literature is limited to mostly retrospective studies. We performed a comprehensive search of the medical literature using PubMed/Medline, EMBASE, and Cochrane reviews on September 13, 2018. We extracted data on clinical outcomes related to benefits (overall [OS] and progression-free [PFS] survival) and harms (relapse and nonrelapse mortality [NRM]) independently by 2 authors. Our search strategy identified 289 references. Five studies (266 patients) were included in this systematic review and meta-analysis. Reduced-intensity and nonmyeloablative regimens were more commonly prescribed (76%). Mobilized peripheral blood stem cells were the preferred graft source (78%). The pooled OS and PFS rates were 59% (95% confidence interval [CI], 50% to 69%) and 36% (95% CI, 27% to 45%), respectively. Pooled relapse rate was 47% (95% CI, 41% to 53%) and pooled NRM rate 19% (95% CI, 13% to 27%). Results of this systematic review and meta-analysis show that allo-HCT yields encouraging OS and PFS rates; however; relapse remains a significant cause of allo-HCT failure. Novel strategies to further improve outcomes should focus on offering allo-HCT before the development of resistant disease and reducing relapse by incorporating post-transplant maintenance therapies.
Topics: Allografts; Disease-Free Survival; Humans; Maintenance Chemotherapy; Mycosis Fungoides; Peripheral Blood Stem Cell Transplantation; Recurrence; Sezary Syndrome; Survival Rate
PubMed: 31494227
DOI: 10.1016/j.bbmt.2019.08.019 -
The Journal of Investigative Dermatology Feb 2020
Meta-Analysis
Topics: Humans; Kaplan-Meier Estimate; Mycosis Fungoides; Prognosis; Skin Neoplasms
PubMed: 31465745
DOI: 10.1016/j.jid.2019.07.712 -
JAMA Dermatology Mar 2019Phototherapy is one of the mainstays of treatment for early mycosis fungoides (MF). The most common modalities are psoralen-UV-A (PUVA) and narrowband UV-B (NBUVB). (Comparative Study)
Comparative Study Meta-Analysis
IMPORTANCE
Phototherapy is one of the mainstays of treatment for early mycosis fungoides (MF). The most common modalities are psoralen-UV-A (PUVA) and narrowband UV-B (NBUVB).
OBJECTIVE
To compare the efficacy and adverse effects of PUVA vs NBUVB in early-stage MF.
DATA SOURCES
A systematic review was performed by searching Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Ovid Medline, PubMed, Cochrane Library, American College of Physicians ACP Journal Club, and Database of Abstracts of Review of Effectiveness from inception to March 30, 2018. UV A, PUVA, mycosis fungoides, Sézary syndrome, cutaneous T-cell lymphoma, UV B, and UVB were used as either key words or MeSH terms.
STUDY SELECTION
Studies of cohorts with histologically confirmed early-stage MF, defined as stages IA, IB, and IIA, that compared PUVA vs NBUVB, had at least 10 patients in each comparator group, and reported outcomes of response to therapy. Exclusion criteria were studies with patients with stage IIB or higher MF, pediatric patients, fewer than 10 in each comparator group, noncomparative studies, case reports, and abstract studies.
DATA EXTRACTION AND SYNTHESIS
The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was followed. Data were pooled using a random-effects model with odds ratio (OR) as effect size.
MAIN OUTCOMES AND MEASURES
Main outcomes were complete response rate, partial response rate, disease recurrence, and adverse effects, including erythema, nausea, pruritus, phototoxic effects, dyspepsia, and pain.
RESULTS
Seven studies were included with a total of 778 patients (405 of 724 [55.9%] men; mean age, 52 years); 527 were treated with PUVA and 251 with NBUVB. Most of the included studies were of poor to moderate quality. Any response was found in 479 of the 527 (90.9%) patients treated with PUVA vs 220 of 251 (87.6%) treated with NBUVB (OR, 1.40; 95% CI, 0.84-2.34; P = .20). Complete response was found in 389 of 527 (73.8%) patients who received PUVA vs 156 of 251 (62.2%) who received NBUVB, which was statistically significant (OR, 1.68; 95% CI, 1.02-2.76; P = .04). Partial response was similar (90 of 501 [18.0%] vs 64 of 233 [27.5%]; OR, 0.58; 95% CI, 0.33-1.04; P = .07). No significant difference was found between PUVA and NBUVB in terms of adverse effects of erythema (38 of 527 [7.2%] vs 17 of 251 [6.7%]; P = .54), nausea (10 of 527 [1.9%] vs 3 of 251 [1.2%]; P = .72), pruritus (2 of 527 [0.4%] vs 4 of 251 [1.7%]; P = .26), phototoxic effects (7 of 527 [1.4%] vs 2 of 251 [0.9%]; P = .72), dyspepsia (6 of 527 [1.2%] vs 0 of 251 [0%]; P = .59), or pain (0 of 527 [0%] vs 2 of 251 [0.9%]; P = .50).
CONCLUSIONS AND RELEVANCE
The findings suggest that PUVA is a potential alternative to NBUVB in the management of early-stage MF. These findings have implications for clinicians involved in the management of early-stage MF.
Topics: Aged; Female; Ficusin; Humans; Male; Middle Aged; Mycosis Fungoides; PUVA Therapy; Prognosis; Skin Neoplasms; Treatment Outcome; Ultraviolet Therapy
PubMed: 30698622
DOI: 10.1001/jamadermatol.2018.5204 -
European Journal of Dermatology : EJD Dec 2018The efficacy of alemtuzumab for the treatment of refractory Sézary syndrome (SS) versus other third-line agents such as pralatrexate and gemcitabine is poorly... (Comparative Study)
Comparative Study
The efficacy of alemtuzumab for the treatment of refractory Sézary syndrome (SS) versus other third-line agents such as pralatrexate and gemcitabine is poorly characterized. To elucidate the effectiveness of alemtuzumab versus other third-line options for the treatment of refractory SS, we conducted a meta-analysis of existing data. A systematic review was performed in March 2017 based on a search using Ovid-MEDLINE and OVID-EMBASE for articles evaluating single-agent alemtuzumab, gemcitabine, or pralatrexate for the treatment of SS and mycosis fungoides (MF). Twenty-two publications were identified that fulfilled all search criteria (total n = 323 patients), with six publications of lower quality being excluded from our analysis in order to decrease the risk of bias (final: n = 308 patients; 93 with SS and 147 with MF). Across all studies, alemtuzumab was significantly more effective in patients with SS (overall response rate [ORR]: 81%; complete response rate [CRR]: 38%) than patients with MF (ORR: 29%; CRR: 8%). However, gemcitabine was more effective than alemtuzumab or pralatrexate in treating MF. Alemtuzumab-treated patients had more frequent side effects, which were influenced by route of administration and dose. There was a lower incidence of lymphopenia and other serious adverse events in patients treated with subcutaneous (38%) compared to intravenous regimens (68%), and lower-dose (5%) compared to high-dose alemtuzumab regimens (54%). No significant differences were found in the effectiveness of different routes of administration or dosing regimens. Our review supports the use of low-dose subcutaneous alemtuzumab as a third-line treatment for SS.
Topics: Alemtuzumab; Aminopterin; Antimetabolites, Antineoplastic; Antineoplastic Agents, Immunological; Deoxycytidine; Folic Acid Antagonists; Humans; Mycosis Fungoides; Retreatment; Sezary Syndrome; Skin Neoplasms; Gemcitabine
PubMed: 30591425
DOI: 10.1684/ejd.2018.3444 -
Giornale Italiano Di Dermatologia E... Dec 2018Mycosis fungoides is the most common cutaneous T cell lymphoma. Selection of appropriate treatment for mycosis fungoides (MF) is based on prognostic factors and overall... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Mycosis fungoides is the most common cutaneous T cell lymphoma. Selection of appropriate treatment for mycosis fungoides (MF) is based on prognostic factors and overall clinical stage at diagnosis. In the past decade, clinical success has been reported using photodynamic therapy (PDT) as an alternative target-specific therapy to treat mycosis fungoides. This review aimed to summarize the current advances in management of mycosis fungoides by administration of photodynamic therapy.
EVIDENCE ACQUISITION
Twenty-four articles, published between 1994 and 2017, were reviewed to assess the efficacy of PDT for MF.
EVIDENCE SYNTHESIS
Methyl-aminolevulinic acid has increased lipophilic properties; red light at around 630 nm achieves deepest and best tissue penetration. However, the total number of PDT sessions depends on the clinical response.
CONCLUSIONS
Further multicenter clinical studies are warranted to assess the cost-effectiveness of PDT.
Topics: Aminolevulinic Acid; Humans; Mycosis Fungoides; Neoplasm Staging; Photochemotherapy; Photosensitizing Agents; Prognosis; Skin Neoplasms; Treatment Outcome
PubMed: 29683282
DOI: 10.23736/S0392-0488.18.05977-1 -
Critical Reviews in Oncology/hematology Jan 2017Brentuximab vedotin (BV) is an antibody-drug conjucate (ADC) comprising a CD30-directed antibody, conjugated to the microtubule-disrupting agent MMAE via a protease... (Review)
Review
BACKGROUND
Brentuximab vedotin (BV) is an antibody-drug conjucate (ADC) comprising a CD30-directed antibody, conjugated to the microtubule-disrupting agent MMAE via a protease cleavable linker. BV is FDA approved for use in relapsed classical Hodgkin lymphoma (HL) and relapsed systemic anaplastic large cell lymphoma (sALCL). There are multiple publications for its utility in other malignancies such as diffuse large B-cell lymphoma (DLBCL), mycosis fungoides (MF), Sézary syndrome (SS), T-cell lymphomas (TCL), primary mediastinal lymphoma (PMBL), and post-transplant lymphoproliferative disorders (PTLD). We believe that BV could potentially provide a strong additional treatment option for patients suffering from NHL.
OBJECTIVE
Perform a systematic review on the use of BV in non-Hodgkin lymphoma (NHL) and other CD30 malignancies in humans.
DATA SOURCES
We searched various databases including PubMed (1946-2015), EMBASE (1947-2015), and Cochrane Central Register of Controlled Trials (1898-2015).
ELIGIBILITY CRITERIA
Inclusion criteria specified all studies and case reports of NHLs in which BV therapy was administered.
INCLUDED STUDIES
A total of 28 articles met these criteria and are summarized in this manuscript.
CONCLUSION
Our findings indicate that BV induces a variety of responses, largely positive in nature and variable between NHL subtypes. With additional, properly powered prospective studies, BV may prove to be a strong candidate in the treatment of various CD30 malignancies.
Topics: Antineoplastic Agents; Brentuximab Vedotin; Clinical Trials, Phase II as Topic; Humans; Immunoconjugates; Lymphoma, Non-Hodgkin; Neoplasm Recurrence, Local; Prospective Studies
PubMed: 28010897
DOI: 10.1016/j.critrevonc.2016.11.009 -
Photodiagnosis and Photodynamic Therapy Mar 2017Mycosis fungoides is the most common cutaneous T-cell lymphoma. It is characterized by slow progress over years to decades, developing from patches to infiltrated... (Review)
Review
Mycosis fungoides is the most common cutaneous T-cell lymphoma. It is characterized by slow progress over years to decades, developing from patches to infiltrated plaques, and sometimes to tumors. Therapies such as localized chemotherapy, photochemotherapy and radiotherapy are often employed when lesions of refractory or relapsing mycosis fungoides are resistant to conventional therapies. However, these methods have acute or chronic side effects and toxicity, which may accumulate with repeated and protracted treatment cycles. Photodynamic therapy is a promising, well-tolerated option for the treatment of localized lesions with excellent cosmetic outcomes. In this article, we systematically reviewed and discussed clinical application of photodynamic therapy in relapsed or refractory mycosis fungoides. There are 20 papers included in this review article.
Topics: Humans; Aminolevulinic Acid; Mycosis Fungoides; Photochemotherapy; Photosensitizing Agents; Skin Neoplasms
PubMed: 27888162
DOI: 10.1016/j.pdpdt.2016.11.010