Allogeneic stem cell transplant for treatment of mycosis fungoides and Sezary syndrome: a systematic review and meta-analysis.

Allogeneic hematopoietic stem cell transplant (allo-HSCT) has been noted to be a potential curative treatment in cases of advanced-stage mycosis fungoides (MF) or Sezary syndrome (SS). To assess outcomes of allo-HSCT for MF/SS we performed a systematic review and meta-analysis including 15 manuscripts and 557 patients, published from 2010-2023. Meta-analysis revealed 1-year and 3+year overall survival (OS) of 51% (95% CI 39-64%) and 40% (32-49%). Progression-free survival at 1 year and 3+years were 42% (31-53%) and 33% (25-42%). Non-relapse mortality was 18% (13-23%). Relapse occurred in of 47% (40-53%) with a median time to relapse of 7.9 months (range 1.6-24 months). Rates of acute and chronic graft-versus-host disease (GVHD) were 45% (35-55%) and 40% (33-48%). Reduced-intensity conditioning (RIC) was associated with superior OS compared to myeloablative conditioning (MAC) (58% vs. 30%, p < 0.001). Of patients with relapse after allo-HSCT, 46% treated with donor lymphocyte infusion (DLI) achieved complete remission. These data support use of allo-HSCT for treatment of advanced-stage MF/SS and suggest superiority of RIC over MAC. Rates of GVHD were comparable to allo-HSCT in general. The improved OS for RIC and high rate of CR with DLI underscore the importance of the graft-versus-lymphoma effect in allo-HSCT for MF/SS.

Phase II Study of Myeloablative 7-8/8-Matched Allotransplantation with Post-Transplantation Cyclophosphamide, Tacrolimus, and Mycophenolate Mofetil.

Graft-versus-host disease (GVHD) is the major toxicity of allogeneic hematopoietic cell transplantation (HCT). We hypothesized that a GVHD prophylaxis regimen of post-transplantation cyclophosphamide (PTCy), tacrolimus (Tac), and mycophenolate mofetil (MMF) would be associated with incidences of acute and chronic GVHD in patients receiving a matched or single antigen mismatched HCT. This Phase II study was conducted at the University of Minnesota using a myeloablative regimen of either total body irradiation (TBI) at a total dose of 1320 cGy, administered in 165-cGy fractions, twice daily from day -4 to day -1, or busulfan (Bu) 3.2 mg/kg daily (cumulative area under the curve, 19,000 to 21,000 µmol/min/L) plus fludarabine (Flu) 40 mg/m2 once daily on days -5 to -2, followed by a GVHD prophylaxis regimen of PTCy 50 mg/kg on days +3 and +4, Tac, and MMF beginning on day +5. The primary endpoint was the cumulative incidence of chronic GVHD necessitating systemic immunosuppression (IST) at 1 year post-transplantation. Between March 2018 and May 2022, we enrolled 125 pediatric and adult patients, with a median follow-up of 813 days. The incidence of chronic GVHD necessitating systemic IST at 1 year was 5.5%. The rate of grade II-IV acute GVHD was 17.1%, and that of grade III-IV acute GVHD was 5.5%. Two-year overall survival was 73.7%, and 2-year graft-versus-host disease-free, relapse-free survival was 52.2%. The 2-year cumulative incidence of nonrelapse mortality was 10.2%, and the rate of relapse was 39.1%. There was no statistically significant difference in survival outcomes between recipients of matched donor transplants versus recipients of 7/8 matched donor transplants. Our data show that myeloablative HCT with PTCy/Tac/MMF results in an extremely low incidence of severe acute and chronic GVHD in well-matched allogeneic HCT.

Phase II Study of Myeloablative 8/8- or 7/8-Matched Allotransplantation with Post-Transplant Cyclophosphamide, Tacrolimus, and Mycophenolate Mofetil: Marked Reduction in GVHD Risk Without Increased Relapse Risk Compared to Historical Cyclosporine/Methotrexate.

Introduction: Graft-versus host disease (GVHD) is a major limitation to the success of allogeneic hematopoietic cell transplant (HCT). We hypothesized that the GVHD prophylaxis regimen of post-transplant cyclophosphamide (PTCy), tacrolimus (Tac) and mycophenolate mofetil (MMF) would reduce the incidence of GVHD in patients receiving a matched or single antigen mismatched HCT without an increase in risk of malignant relapse. Methods: This is a phase II study conducted at the University of Minnesota using a myeloablative regimen of either: (A) total body irradiation (TBI, total dose 1320 cGy, administered in 165 cGy fractions, twice a day from days -4 to -1) or (B) Busulfan 3.2mg/kg daily (cumulative AUC 19,000 - 21,000 µmol/min/L) plus fludarabine 160mg/m2 days -5 to -2, followed by a GVHD prophylaxis regimen of PTCy (50mg/kg days +3 and +4), Tac and MMF (beginning day +5). The primary endpoint is cumulative incidence of chronic GVHD requiring systemic immunosuppression at 1-year post-transplant. We compared results to our previous myeloablative protocol for matched donors utilizing cyclosporine/methotrexate (CSA/MTX) GVHD prophylaxis. Results: From March 2018 - June 2022, we enrolled and treated 125 pediatric and adult patients with a median follow up of 472 days. Grade II-IV acute GVHD occurred in 16% (95% confidence interval (CI): 9-23%); Grade III-IV acute GVHD was 4% (CI: 0-8%). No patients experienced grade IV GVHD, and there were no deaths due to GVHD before day 100. Only 3 developed chronic GVHD requiring immune suppression, (4%, CI: 0-8%). Two-year overall survival (OS) was 80% (CI: 69-87%), and (graft-versus-host disease-free, relapse-free survival) GRFS 57% (CI: 45-67%), both higher than historical CSA/MTX. The incidence of grade II-IV aGVHD, cGVHD, and NRM were all lower with PTCy/Tac/MMF compared to historical CSA/MTX. One-quarter (25%) experienced relapse (CI: 15-36%) similar to historical CSA/MTX. There was no statistically significant difference in survival outcomes between recipients of matched versus 7/8 donors. Conclusion: Myeloablative HCT with PTCy/Tac/MMF results in extremely low incidence of severe acute or chronic GVHD, the primary endpoint of this clinical trial. Relapse risk is not increased compared to our historical CSA/MTX cohort.

A Practical Review of the Presentation, Diagnosis, and Management of Cutaneous B-Cell Lymphomas.

This review of cutaneous B-cell lymphoma (CBCL) is focused on the clinical presentation, treatment, and workup of each type of lymphoma. Part 1 is an overview of each of the CBCLs, including clinical presentation, recent advances in the pathobiology, and evidence regarding treatment strategies. Part 2 is a detailed guide to the steps in diagnosis and workup of a newly diagnosed CBCL according to the International Society for Cutaneous Lymphoma/European Organization for Research and Treatment of Cancer and NCCN guidelines.

Changing patterns of multidisciplinary team treatment, early mortality, and survival in colorectal cancer.

BACKGROUND: This study reports early mortality and survival from colorectal cancer in relation to the pattern of treatments delivered by the multidisciplinary team (MDT) meeting at a high-volume institution in England over 14 years. METHODS: All patients diagnosed with colorectal cancer and discussed during MDT meetings from 2003 to 2016 at a single institution were reviewed. Three time intervals (2003-2007, 2008-2012, and 2013-2016) were compared regarding initial surgical management (resection, local excision, non-resection surgery, and no surgery), initial oncological therapy, 90-day mortality, and crude 2-year survival for the whole cohort. Sub-analyses were performed according to age greater or less than 80 years. RESULTS: The MDT managed 4617 patients over 14 years (1496 in the first interval and 1389 in the last). Over this time, there was a reduction in emergency resections from 15.5 per cent to 9.0 per cent (P < 0.0001); use of oncological therapies increased from 34.6 per cent to 41.6 per cent (P < 0.0001). The 90-day mortality after diagnosis of colorectal cancer dropped from 14.8 per cent to 10.7 per cent (P < 0.001) and 2-year survival improved from 58.6 per cent to 65 per cent (P < 0.001). Among patients aged 80 years or older (425 and 446, in the first and last intervals respectively) there was, in addition, a progressive increase in 'no surgery' rate from 33.6 per cent to 50.2 per cent (P < 0.0001) and a reduction in elective resections from 42.4 per cent to 33.9 per cent (P = 0.010). The 90-day mortality after elective resection fell from 10.0 per cent (18 of 180) to 3.3 per cent (5 of 151; P = 0.013). CONCLUSIONS: Survival from colorectal cancer improved significantly over 14 years. Among patients aged ≥80 years, major changes in the type of treatment delivered were associated with a decrease in postoperative mortality.

The significance of epidermal involvement in primary cutaneous gamma/delta (γδ) T-cell lymphoma: A systematic review and meta-analysis.

BACKGROUND: Primary cutaneous gamma/delta (γδ) T-cell lymphoma (PCGDTCL) is a rare, aggressive peripheral T-cell lymphoma. There is evidence that patients with epidermotropic PCGDTCL may have an improved prognosis compared with those with only dermal and/or subcutaneous involvement. METHODS: Systematic review of the literature and application of inclusion criteria yielded 48 manuscripts detailing the cases of 104 patients. RESULTS: Of the 104 patients, 57 were male (51.4%) and 47 were female (48.5%) Based on provided histopathologic descriptions, 57 cases (54.8%) had no epidermotropism, 47 cases (45.2%) patients demonstrated any degree of epidermotropism, and 25 cases were predominantly epidermotropic (25/104, 24%). Five-year overall survivals for patients with no epidermotropism, any epidermotropism, and predominantly epidermotropic presentation were 32.8%, 28.9%, and 40.0%, respectively (p = 0.40). The most commonly performed immunohistochemical markers were CD3, CD4, CD8, CD5, CD7, CD30, CD56, TCR beta, TCR γ, and TCR δ. There was no statistically significant difference in immunophenotype between groups. Lesion morphology was described in the majority of cases (85/104, 80.9%); most cases presented as a combination of nodules, plaques, and tumors (77.4%). Several cases had more atypical presentations, including "mycosis-fungoides-like" and ulcerated. CONCLUSION: In PCGDTCL, neither epidermotropism nor predominantly epidermotropic phenotype predict a better prognosis. In addition, the case report literature in dermatology and dermatopathology is rich and highly valuable.

Surgical management and lymph-node biopsy of rare malignant cutaneous adnexal carcinomas: a population-based analysis of 7591 patients.

OBJECTIVE: To analyze the prognosis of cutaneous adnexal malignancies, survival relative to surgical management, and utility of lymph-node biopsy. DESIGN: Population-based study of the SEER-18 database from 1975 to 2016. PARTICIPANTS: 7591 patients with sweat gland carcinoma, hidradenocarcinoma, spiradenocarcinoma, sclerosing sweat duct tumor/microcystic adnexal tumor (SSDT/MAC), porocarcinoma, eccrine adenocarcinoma, and sebaceous carcinoma RESULTS: Five-year OS ranged from 68.0 to 82.6%, while 5-year DSS ranged from 94.6 to 99.0%. The majority of patients were treated with narrow (42.4%) or wide local excision (16.9%). DSS at 5 years showed that patients with stage IV had significantly poorer survival (50.3%) than I, II, or III (99.3%, 97.8%, and 89.0% respectively). 5-year OS was significantly higher for narrow excision (excision with < 1 cm margin, 78.5%) than observation (65.0%), excisional biopsy (66.8%), or wide local excision (WLE, 73.2%). Lymph-node biopsy was performed in a minority of cases (8.1%) and patients showed no significant difference in survival based on nodal status. The sensitivity and specificity of lymph-node biopsy for all malignancies were 46% and 80%, respectively. The PPV and NPV for that group were 0.46 and 0.80, respectively. Invasion of deep extradermal structures was a poor predictor of nodal positivity. CONCLUSIONS: These malignancies have excellent DSS. Narrow excisions demonstrate better 5-year DSS and OS compared with WLE. Lymph-node biopsy is a poor predictor of survival in advanced stage disease and utility is limited.

Cutaneous T-cell lymphoma is associated with increased risk of lymphoma, melanoma, lung cancer, and bladder cancer.

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.

Hand-foot skin reaction with primarily dorsal involvement in a patient with metastatic renal cell carcinoma on cabozantinib.

A 61-year-old man with metastatic renal cell carcinoma on cabozantinib developed hand-foot skin reaction with predominantly dorsal involvement including painful violaceous plaques over the joints and keratotic yellow plaques on the palmar fingers. The medication was discontinued with resolution of the plaques and later reinitiated at a lower dose uneventfully.

Increased risk of second primary hematologic and solid malignancies in patients with mycosis fungoides: A Surveillance, Epidemiology, and End Results analysis.

BACKGROUND: Mycosis fungoides (MF) is associated with increased risk of second primary hematologic malignancies, but its association with second primary solid tumors is less well characterized. OBJECTIVE: This retrospective analysis seeks to assess the risk of being diagnosed with a second primary hematologic or solid malignancy in patients with MF. DESIGN: We performed an analysis of patients diagnosed with MF from 2000 through 2015 in the United States cancer registries of SEER-18 (N = 6742). RESULTS: Relative risks were estimated by using standardized incidence ratios (SIRs). Among 6742 patients, there were 511 (7.5%) second cancer events (SIR, 10.15; 95% confidence interval [CI], 9.29-11.07). These included 184 (36.0%) hematologic malignancies (SIR, 39.71; 95% CI, 34.05-46.05) and 327 (64.0%) solid tumor malignancies (SIR, 7.33; 95% CI, 6.56-8.17). Patients with MF were at increased risk for non-Hodgkin lymphoma; Hodgkin lymphoma; melanoma; and lung, female breast, prostate, colon, and renal cancers. Females were at higher risk than males (P < .05). All ethnic groups showed a statistically significant elevation in SIRs. Elevation of SIRs was observed across all stages of MF. CONCLUSIONS AND RELEVANCE: Patients with MF are at increased risk for diagnosis of second primary malignancies and should be carefully screened for discernable signs and symptoms of second malignancies.

Multimodal neuromarkers in schizophrenia via cognition-guided MRI fusion.

Cognitive impairment is a feature of many psychiatric diseases, including schizophrenia. Here we aim to identify multimodal biomarkers for quantifying and predicting cognitive performance in individuals with schizophrenia and healthy controls. A supervised learning strategy is used to guide three-way multimodal magnetic resonance imaging (MRI) fusion in two independent cohorts including both healthy individuals and individuals with schizophrenia using multiple cognitive domain scores. Results highlight the salience network (gray matter, GM), corpus callosum (fractional anisotropy, FA), central executive and default-mode networks (fractional amplitude of low-frequency fluctuation, fALFF) as modality-specific biomarkers of generalized cognition. FALFF features are found to be more sensitive to cognitive domain differences, while the salience network in GM and corpus callosum in FA are highly consistent and predictive of multiple cognitive domains. These modality-specific brain regions define-in three separate cohorts-promising co-varying multimodal signatures that can be used as predictors of multi-domain cognition.

Reducing behavioural risk factors for cancer: An affect regulation perspective.

Nearly half of all cancer deaths are attributable to preventable causes, primarily unhealthy behaviours such as tobacco use, alcohol use and overeating. In this review, we argue that people engage in these behaviours, at least in part, as a means of regulating their affective states. To better understand why people engage in these behaviours and how researchers might design interventions to promote the selection of healthier methods for regulating affect, we propose a conceptual model of affect regulation. We synthesise research from both the stress and coping tradition as well as the emotion and emotion regulation tradition, two literatures that are not typically integrated. In so doing, we indicate where researchers have made headway in understanding these behaviours as affect regulation and note how our model could be used to structure future work in a way that would be particularly advantageous to cancer control efforts.

Laparoscopic surgical treatment of ileocecal Crohn's disease: Impact of obesity on short term results. / Cirugía laparoscópica en el tratamiento de la enfermedad de Crohn del área ileocecal: impacto de la obesidad en los resultados postoperatorios inmediatos.

INTRODUCTION: The aim of our study was to analyse the short-term outcomes of laparoscopic surgery for a no medical responding ileocolic Cohn's disease in a single centre according to the presence of obesity. METHODS: A cross-sectional study was performed including all consecutive patients who underwent laparoscopic resection for ileocecal Crohn's disease from November 2006 to November 2015. Patients were divided according to body mass index ≥ 30 kg/m2 in order to study influence of obesity in the short-term outcomes. The following variables were studied: characteristics of patients, surgical technique and postoperative results (complications, reintervention, readmission and mortality) during first 30 postoperative days. RESULTS: A total of 100 patients were included (42 males) with a mean age of 39.7±15.2 years (range 18-83). The overall complication rate was 20% and only 3 patients had an anastomotic leak. Seven patients needed reoperation in the first 30 days postop (7%). The median postoperative length of hospitalization was 5.0 days. Operative time was significantly longer in patients with obesity (130 vs. 165minutes, P=.007) but there were no significant differences among the postoperative results in patients with and without obesity. CONCLUSIONS: This study confirmed that laparoscopic approach for ileocecal Cohn's disease is a safety and feasible technique in patients with obesity. In this last group of patients we only have to expect a longer operative time.