Multiple Poor Prognostic Factors Research Articles

Initial Treatment with Biological Therapy in Rheumatoid Arthritis.

We aimed to analyse the effectiveness, efficiency, and safety of initial treatment with biological therapies in rheumatoid arthritis (RA). Qualitative study. A group of RA experts was selected. A scoping review in Medline was conducted to analyse the evidence of initial RA treatment with biological therapies. Randomised clinical trials were selected. Two reviewers analysed the articles and compiled the data, whose quality was assessed using the Jadad scale. The experts discussed the review's findings and generated a series of general principles: Results: Seventeen studies were included. Most of the included patients were middle-aged women with early RA (1-7 months) and multiple poor prognostic factors. Initial treatment with TNF-alpha inhibitors combined with methotrexate (MTX) and an IL6R inhibitor (either in mono or combination therapy) is effective (activity, function, radiographic damage, quality of life), safe, and superior to MTX monotherapy in the short and medium term. In the long term, patients who received initial treatment with biologicals presented better results than those whose initial therapy was with MTX. Initial treatment of RA with biological therapies is effective, efficient, and safe in the short, medium, and long term, particularly for patients with poor prognostic factors.

Prevention of Radiographic Progression in Higher-Risk Patients with Rheumatoid Arthritis Using Filgotinib in PhaseIII Studies: Narrative Review of PostHoc Analyses.

Filgotinib is an oral preferential Janus kinase1 inhibitor that demonstrated significant reductions in radiographic progression, with an acceptable tolerability and safety profile, vs placebo in patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX-IR; FINCH1) and vs MTX in MTX-naïve patients with RA (FINCH3). International treatment guidelines identify multiple poor prognostic factors (PPFs) associated with worse disease outcomes among patients with RA. However, questions remain both about the clinical utility of considering PPFs and about which PPFs should drive treatment decisions. Additionally, the role of radiographic findings in clinical practice continues to be discussed and to evolve. This review examines radiographic results from posthoc analyses of phase3 trials of filgotinib that examined subgroups with 4PPFs or with baseline estimated rapid radiographic progression (e-RRP). In MTX groups, there were trends toward greater progression among patients with 4PPFs or e-RRP, suggesting these subgroups may comprise a higher-risk population. Results show general consistency for the efficacy of filgotinib 200mg plus MTX vs placebo plus MTX/MTX monotherapy on radiographic assessments, including change from baseline in modified total Sharp score and proportions without radiographic progression, even among MTX-IR or MTX-naïve patients with 4PPFs or e-RRP who may be at higher risk of bone damage. Multivariate analysis identified multiple factors associated with baseline e-RRP status. This summary of the current understanding of benefits associated with filgotinib on radiographic progression and the relevance of baseline factors to these benefits may help inform treatment decisions for patients facing high risk of radiographic progression.

Amidst the chaos of late rheumatoid arthritis with no treatment

A 78-year-old man with 24 years history of Rheumatoid Arthritis (RA) came with neck pain. He always refused any treatment except for NSAIDs. From 2 years ago, he was bedridden. He was chronic cigarette smoker. On examination, he had rheumatoid nodules, severe both hands deformity, elbows flexion contracture and knee joints limitation of motion. His lab tests showed high titer of rheumatoid factor and anti cyclic citrullinated protein antibody, high ESR, CRP and vitamin D deficiency. Radiologic studies showed multiple vertebral osteoporotic fractures. Cervical spine CT scan (a and b) showed destruction of the odontoid process and fusion of facet joints of the C2, C3 and C4. MRI of cervical spine (c) showed destruction of odontoid process surrounding by inflammatory synovitis. CT scan of lung (e and f) showed multiple upper lobeand sub pleural nodules along fibrotic changes in base of right lobe. X-ray of knee and hip (d and g) showed severe osteoarthritis andsite of previouship nailing. The patient was diagnosed with advanced erosive nodular RA, severe secondary osteoporosis, osteoarthritis and rheumatoid lung. Standard treatment was recommended, although he again refused. RA can result in progressive joint destruction, deformity and disability [1]. In the spine, it has a predilection for the cervical area, leads to odontoid erosion, spinal instability, and subluxation. In the era of importance of early treatment, these complications are rarely seen, however despite biologic therapy, it has been shown that 15-30% of RA patients can still have preclinical cervical spine abnormalities [2]. The Osteoporosis (OP) is more frequent in patients with high disease activity, bone erosions, >10 years disease duration, and high titers of anti-CCP and RF positivity [3]. Our patient with multiple poor prognostic factors for erosive RA came with extra articular and complications of this disease due refusing treatment.

Efficacy and safety of filgotinib in methotrexate-naive patients with rheumatoid arthritis with poor prognostic factors: post hoc analysis of FINCH 3

ObjectiveThis analysis evaluated efficacy and safety of filgotinib, a Janus-associated kinase 1-preferential inhibitor, in methotrexate (MTX)-naive patients with rheumatoid arthritis (RA) with multiple poor prognostic factors (PPFs).MethodsThis was a post...

Preoperative evaluation and indications for pulmonary metastasectomy.

Pulmonary metastasectomy (PM) is an established treatment that can provide improved long-term survival for patients with metastatic tumor(s) in the lung. In the current era, where treatment options other than PM such as stereotactic body radiation therapy (SBRT), immunotherapy, and molecular-targeted therapy are available, thoracic surgeons should review the approach to the preoperative evaluation and the indications. Preoperative evaluation consists of history and physical examinations, physiological tests, and radiological examinations. Radiological examinations serve to identify the differential diagnosis of the pulmonary nodules, evaluate their precise number, location, and features, and search for extra thoracic metastases. The indication of PM should be considered from both physiological and oncological points of view. The general criteria for PM are as follows; (I) the patient has a good general condition, (II) the primary malignancy is controlled, (III) there is no other extrapulmonary metastases, and (IV) the pulmonary lesion(s) are thought to be completely resectable. In addition to the general eligibility criteria of PM, prognostic factors of each tumor type should be considered when deciding the indication for PM. When patients have multiple poor prognostic factors and/or a short disease-free interval (DFI), thoracic surgeons should not hesitate to observe the patient for a certain period before deciding on the indication for PM. A multidisciplinary discussion is needed in order to decide the indication for PM.

Expression of HMGB1 protein in breast cancer and its clinicopathological significance

Objective: To investigate the expression and clinicopathological significance of high mobility group box protein B1 (HMGB1) protein in breast cancer. Methods: The expression of HMGB1 protein in 26 normal breast tissues and 417 invasive breast cancer tissues diagnosed at Dongyang People's Hospital, Zhejiang Province from 2016 to 2018 were detected by immunohistochemical EnVision method. The relationship between nuclear and cytoplasmic HMGB1 protein expression and clinicopathologic features of breast cancer patients were analyzed. Results: The nuclear and cytoplasmic expression of HMGB1 protein was 80.8% (337/417) and 16.8% (70/417) respectively in breast cancer, and was 46.2%(12/26) and 0(0/26) respectively in normal breast tissue. Both nuclear and cytoplasmic expression of HMGB1 protein in breast cancer were significantly higher than normal breast tissue (P<0.001, P=0.046, respectively). The nuclear expression of HMGB1 protein was also higher in high grade, estrogen receptor (ER) negative, progesterone receptor (PR) negative (P=0.006, P=0.004, P<0.001, respectively); whereas the cytoplasmic expression of HMGB1 protein was also higher in high grade, estrogen receptor (ER) negative, progesterone receptor (PR) negative (P<0.001 in all) breast cancers. Multivariate logistic regression model showed that nuclear HMGB1 expression correlated with histologic grade (OR=2.188, 95%CI=1.078-4.443, P=0.030), while cytoplasmic HMGB1 expression correlated with histologic grade (OR=3.031, 95%CI=1.600-5.742, P=0.001), ER (OR=0.129, 95%CI=0.034-0.494, P=0.003) and TNM staging (OR=3.820, 95%CI=1.042-14.001, P=0.043). Multivariate analysis of Cox proportional hazard model showed that nuclear HMGB1 expression was an independent risk factor for the overall survival of breast cancer patients (HR=0.366, 95%CI=0.138-0.972, P=0.044). Conclusion: Nuclear and cytoplasmic HMGB1 proteins are related to multiple poor prognostic factors in breast cancer, and may be a potential biomarker for breast cancer treatment.

Efficacy of Abatacept and Adalimumab in Patients with Early Rheumatoid Arthritis With Multiple Poor Prognostic Factors: Post Hoc Analysis of a Randomized Controlled Clinical Trial (AMPLE).

IntroductionPatients with rheumatoid arthritis (RA) with poor prognostic factors, such as seropositivity for anti-citrullinated protein antibodies and early erosions, may benefit from early intensive treatment. However, information to guide physicians on the best choice of therapy in these patients is limited. The objective of this study was to describe the efficacy of subcutaneous abatacept versus adalimumab over 2 years in patients with seropositive, erosive early RA in the AMPLE study.MethodsThis exploratory post hoc analysis compared clinical, functional and radiographic outcomes in two subsets of patients: patients with early RA (≤ 6 months’ disease duration) who were seropositive for rheumatoid factor and/or anti-citrullinated protein antibodies and had > 1 radiographic erosion (Cohort 1); and patients with RA and absence of ≥ 1 of these inclusion criteria (Cohort 2).ResultsOf the 646 randomized patients, Cohort 1 included 38 patients receiving abatacept and 45 receiving adalimumab, and Cohort 2 included 280 patients receiving abatacept and 283 receiving adalimumab. Baseline demographics and disease characteristics were generally similar between treatment groups in both cohorts. Over 2 years, in Cohort 1, the adjusted mean change from baseline in the Disease Activity Score in 28 joints (using C-reactive protein) was numerically greater for abatacept than for adalimumab (mean difference at day 365 was 0.9, 95% confidence interval − 1.47 to − 0.33). Similar patterns of improvement were observed for other disease activity measures and physical function, but not for radiographic outcomes. No treatment-related differences were observed in Cohort 2.ConclusionThis analysis indicates a trend towards improved disease activity and physical function with abatacept versus adalimumab in patients with seropositive, erosive early RA.Trial RegistrationClinicalTrials.gov NCT00929864.FundingBristol-Myers Squibb.Electronic Supplementary MaterialThe online version of this article (10.1007/s40744-019-00174-7) contains supplementary material, which is available to authorized users.

Proton beam therapy versus stereotactic body radiotherapy for hepatocellular carcinoma: practice patterns, outcomes, and the effect of biologically effective dose escalation.

Stereotactic body radiation therapy (SBRT) and proton beam therapy (PBT) generally are safe and effective for non-operative hepatocellular carcinoma (HCC). To date, data comparing the two modalities are limited. We aimed to identify the practice patterns and outcomes of nonsurgical HCC cases treated definitively with either SBRT or PBT. We queried the National Cancer Database for T1-2N0 HCC patients receiving PBT or SBRT from 2004 to 2015. Patients were excluded for any treatment other than non-palliative external beam radiotherapy. A multivariable binomial regression model identified patterns of SBRT/PBT use, and propensity-matched multivariable Cox regression assessed correlates of survival. A total of 71 patients received PBT and 918 patients received SBRT (median follow-up 45 months). SBRT was used in 1.8% of nonoperative early stage HCC cases in 2004 and 4.2% of cases in 2015, whereas PBT was used in 0.1-0.2% of cases every year. The median biologically effective dose (BED) for SBRT and PBT was 100 Gy10 and 98 Gy10, respectively (OR =0.70, P=0.17). Factors predictive of receiving PBT included: white race, higher comorbidity score, higher education, metropolitan residence, tumors >5 cm and recent treatment (all P<0.05). Both PBT (HR =0.48, 95% CI: 0.29-0.78) and BED ≥100 Gy10 (HR =0.61, 95% CI: 0.38-0.98) were independent predictors for longer survival. Although not implying causation and requiring prospective corroboration, PBT was independently associated with longer survival than SBRT, despite being delivered to HCC patients with multiple poor prognostic factors. PBT may also allow for safer BED escalation, which also independently associated with outcomes.

The Use of Liquid Biopsies in Patients With NSCLC

The Use of Liquid Biopsies in Patients With NSCLC

Anaplastic carcinoma of thyroid gland with widespread soft tissue metastasis: an unusual presentation

Anaplastic thyroid cancer is the rarest tumour of the thyroid gland, representing only 2% of clinically recognised thyroid cancers. The most common metastatic sites are lungs, followed by the intrathoracic...

Outcomes and prognostic factors of localized, resected malignant salivary gland tumors: Examining a single institution’s 12-year experience to discover indications for adjuvant chemotherapy.

e17587 Background: Survival outcomes remain poor in salivary gland malignancies (SGMs) with multiple poor prognostic factors despite adjuvant radiotherapy. We examined prognostic factors that portended poor survival in resected SGMs to determine possible indications for adjuvant chemoradiotherapy. Methods:Patients who underwent curative resection with or without adjuvant radiotherapy between 2002 and 2014 were identified and retrospective chart review was performed. Bivariate analysis was performed on continuous variables using Analysis of Variance. Chi-Square analysis and Fishers Exact Tests were performed on categorical variables. To evaluate the overall survival (OS) and disease-free survival (DFS), Kaplan-Meier curves and log-rank tests of homogeneity were used. Results: Overall, 99 patients met inclusion criteria. Median follow-up time was 46.8 months. Univariate analysis revealed male sex, smoking history ≥ 10 pack-years, high grade, stage III-IVB, squamous cell histology, and perineural invasion significantly impacted OS and DFS. High-risk histopathology significantly impacted DFS and trended towards poor OS. Positive resection margins trended towards significantly impacting DFS. Multivariate analysis revealed only male sex and perineural invasion significantly impacted OS and DFS. Conclusions: Survival outcomes remain poor for patients with high-grade, late-stage tumors with perineural invasion. Specifically, perineural invasion is a poor prognostic factor regardless of age, histology, stage, and grade. Males and patients with a smoking history ≥ 10 pack-years have worse survival outcomes with male sex being a more influential prognostic factor. Notably, this is the first study to quantify patient’s smoking history in malignant salivary gland tumors and assess the impact of pack-year smoking history on survival outcomes. Given our observed trend, positive resection margins would likely become significant influencer of DFS with larger sample size and longer follow up. Adjuvant chemoradiotherapy should be evaluated in patients with the above-mentioned characteristics.

Chemotherapy and molecular targeting therapy for recurrent cervical cancer.

For patients with primary stage ⅣB, persistent, or recurrent cervical cancer, chemotherapy remains the standard treatment, although it is neither curative nor associated with long-term disease control. In this review, we summarized the history of treatment of recurrent cervical cancer, and the current recommendation for chemotherapy and molecular targeted therapy. Eligible articles were identified by a search of the MEDLINE bibliographical database for the period up to November 30, 2014. The search strategy included the following any or all of the keywords: “uterine cervical cancer”, “chemotherapy”, and “targeted therapies”. Since cisplatin every 21 days was considered as the historical standard treatment for recurrent cervical cancer, subsequent trials have evaluated and demonstrated activity for other agents including paclitaxel, gemcitabine, topotecan and vinorelbine among others. Accordingly, promising agents were incorporated into phase Ⅲ trials. To examine the best agent to combine with cisplatin, several landmark phase Ⅲ clinical trials were conducted by Gynecologic Oncology Group (GOG) and Japan Clinical Oncology Group (JCOG). Through, GOG204 and JCOG0505, paclitaxel/cisplatin (TP) and paclitaxel/carboplatin (TC) are now considered to be the recommended therapies for recurrent cervical cancer patients. However, the prognosis of patients who are already resistant to chemotherapy, are very poor. Therefore new therapeutic strategies are urgently required. Molecular targeted therapy will be the most hopeful candidate of these strategies. From the results of GOG240, bevacizumab combined with TP reached its primary endpoint of improving overall survival (OS). Although, the prognosis for recurrent cervical cancer patients is still poor, the results of GOG240 shed light on the usefulness of molecular target agents to chemotherapy in cancer patients. Recurrent cervical cancer is generally considered incurable and current chemotherapy regiments offer only modest gains in OS, particularly for patients with multiple poor prognostic factors. Therefore, it is crucial to consider not only the survival benefit, but also the minimization of treatment toxicity, and maximization of quality of life (QOL).

Aggressive presentation of multiple myeloma as renal failure and pathological fracture of dorsal vertebra in a young patient: a rare case report

Multiple myeloma presenting with acute renal failure with dorsal vertebral fracture is extremely rare phenomenon. Renal failure in multiple myeloma is associated with Light chain myeloma, serum creatinine more than 4mg/dL, extensive proteinuria and early infections. Our patient was a 29 -year-old male with multiple poor prognostic factors for renal failure. He presented with sudden onset pain in the backbone with weakness of lower extremities and loss of bowel and bladder control. On neurological examination – power of lower extremities was 4/5 with sign of sensory deficit at below umbilicus. He was diagnosed as lamda type nonsecretory multiple myeloma. He was started with malphalalan-prednisolone regimen but succumb to his disease process after one week.

Elderly patients with glioblastoma multiforme treated with concurrent temozolomide and standard- versus abbreviated-course radiotherapy.

Glioblastoma multiforme (GBM) is an aggressive neoplasm, with controversy regarding treatment in elderly patients. To review outcomes of elderly patients aged ≥ 65 with newly diagnosed GBM treated with concurrent temozolomide and either standard-course radiotherapy (SRT) or abbreviated-course radiotherapy (ART). Retrospective review from 2003 to 2012. Survival, comparing treatment regimens. One hundred patients received SRT (median dose = 60 Gy), and 29 received ART (median dose = 35 Gy). O6- methylguanine-DNA methyltransferase (MGMT) status was available for 26 SRT and 13 ART recipients. Median age was 70 years. Median follow-up was 11 months. At analysis, 3 patients were alive. Multivariate analysis of the entire cohort found SRT (hazard ratio [HR] = 0.421, p = 0.0001), Karnofsky Performance Score of 70 or higher (HR = 1.894, p = 0.0031), and more extensive surgery (HR = 0.466, p = 0.0023) were associated with longer survival time, but age was not. Median time to death with SRT was 13 months versus 5.4 months with ART, but the latter had worse prognostic factors, including lower Karnofsky Performance Scores, fewer gross total resections, and higher recursive partitioning analysis class. Recipients of SRT with methylated MGMT promoter had a trend toward longer survival compared with unmethylated MGMT (p = 0.06), but ART recipients had shorter survival with MGMT methylation (p = 0.02). Elderly patients with multiple poor prognostic factors given ART had short survival times. Relative to other variables, MGMT status may not predict outcome for these patients.

Case report on renal failure reversal in lambda chain multiple myeloma with bortezomib and dexamethasone.

Renal failure (RF) reversal in multiple myeloma (MM) is associated with an improved prognosis. Light chain myeloma, serum creatinine (SCr) > 4 mg/dL, extensive proteinuria, early infections, and certain renal biopsy findings are associated with lower rates of RF reversal. Our patient is a 67-year-old female with multiple poor prognostic factors for RF reversal who demonstrated a rapid renal response with bortezomib and dexamethasone (BD) regimen. She presented initially with altered mental status. On exam, she appeared lethargic and dehydrated and had generalized tenderness. She had been taking ibuprofen as needed for pain for a few weeks. Labs showed a white cell count—18,900/μL with no bandemia, hemoglobin 10.8 gm/dL, potassium—6.7 mEq/L, bicarbonate—15 mEq/L, blood urea nitrogen—62 mg/dL, SCr—5.6 mg/dL (baseline: 1.10), and corrected calcium—11.8 mg/dL. A rapid flu test was positive. Imaging studies were unremarkable. Her EKG showed sinus tachycardia and her urinalysis was unremarkable. The unexplained RF in an elderly individual in conjunction with hypercalcemia and anemia prompted a MM work-up; eventually, lambda variant MM was diagnosed. An immediate (4 days) renal response defined as 50% reduction in SCr was noticed after initiation of the BD regimen.

Quality of life in patients with advanced renal cell carcinoma treated with temsirolimus or interferon-α

Background:Temsirolimus was approved in Europe as first-line treatment of poor-prognosis advanced renal cell carcinoma (advRCC) based on significant clinical benefits.Methods:Patients with advRCC and multiple poor-prognostic factors were randomly assigned to receive 25 mg intravenous temsirolimus weekly, interferon-α (titrated to 18 mU) three times weekly, or 15 mg intravenous temsirolimus weekly plus 6 mU of interferon-α three times weekly. EuroQol-5D utility score (EQ-5D index) and the EQ-5D visual analogue scale (EQ-VAS) responses were recorded. For analysis, patients were required to have their EQ-5D data recorded at baseline, week 12, and last visit after week 12. The analysis was conducted using last-visit data and a repeated-measures mixed-effect (RMME) model to evaluate quality-of-life differences between temsirolimus and interferon-α, controlling for baseline covariates.Results:Average EQ-5D score at the last measure was significantly higher in patients receiving temsirolimus compared with interferon-α: by 0.10 on EQ-5D index (P=0.0279) and by 6.61 on EQ-VAS (P=0.0095). In the RMME model, the least-square mean for on-treatment EQ-5D index score was 0.590 with temsirolimus and 0.492 with interferon-α (P=0.0022).Conclusion:Temsirolimus is associated with significantly higher EQ-5D scores compared with interferon-α in patients with previously untreated poor-prognosis advRCC.

Refractory Plasmablastic Type Myeloma with Multiple Extramedullary Plasmacytomas and Massive Myelomatous Effusion: Remarkable Response with a Combination of Thalidomide and Dexamethasone

A 74-year-old man with multiple myeloma was refractory to melphalan/prednisolone (MP), high-dose dexamethasone and VAD chemotherapy. He had the following poor prognostic factors: 1) multiple extramedullary plasmacytomas, 2) massive myelomatous effusion, 3) increasing immature myeloma cells with plasmablastic morphology, and 4) predominance of MPC1-CD49e-CD45+ phenotype immature myeloma cells. Combination therapy with thalidomide and dexamethasone resulted in a rapid response and a partial remission despite his multiple poor prognostic factors. The present case suggests that combination therapy with thalidomide and dexamethasone is still an alternative treatment regimen for resistant extramedullary plasmacytoma with a plasmablastic morphology.

Long-term Complete Remission in a 71-year-old Patient with AML-M7 after Low-dose Cytarabine Induction and Intermediate-dose Cytarabine Consolidation Treatment

The authors describe the case of a 71-year-old patient with acute megakaryocytic leukemia (AML-M7) who was successfully treated with low-dose cytarabine induction followed by intermediate-dose cytarabine consolidation therapy. The patient presented with infection and rapidly increasing blood blasts. The diagnosis was consistent with AML-M7 with a normal karyotype. Peripheral blood blasts decreased rapidly upon low-dose cytarabine administration, and the patient achieved complete remission after two courses of low-dose cytarabine (10 bid for 12 days). Consolidation therapy with intermediate-dose cytarabine (1.0 bid on day 1, 3 and 5) was then instituted without serious complication. He remained in complete remission at the time of writing 47 month after diagnosis. In spite of multiple poor prognostic factors, this patient showed excellent treatment outcome through low-dose cytarabine induction and intermediate-dose cytarabine consolidation. It needs to be validated whether acute leukemia with a megakaryocytic morphology is exceptionally sensitive to cytarabine.

Successful Salvage with High-Dose Sequential Chemotherapy Coupled with In Vivo Purging and Autologous Stem Cell Transplantation in 2 Patients with Primary Refractory Mantle Cell Lymphoma Presenting in the Leukemic Phase

We report the results of an aggressive salvage regimen in 2 patients with advanced-stage leukemic-phase mantle cell lymphoma who were refractory to previous conventional therapies. We combined multiple phases of a cytoreductive regimen including rituximab and sequential high-dose treatment with autologous stem cell transplantation (ASCT). The regimen consisted of a debulking phase with fludarabine, idarubicin, high-dose cytarabine, and high-dose methotrexate; a mobilization and in vivo purging phase with rituximab, cyclophosphamide, and granulocyte colony-stimulating factor; high-dose sequential chemotherapy with etoposide, mitoxantrone, and melphalan followed by ASCT; and, finally, posttransplantation consolidation with rituximab for treatment of minimal residual disease. With this regimen, these 2 refractory patients with multiple poor prognostic factors are in complete remission at 41 and 42 months following transplantation. Although the fact that these 2 patients are still in remission beyond 3 years after ASCT is encouraging, we need a longer follow-up to comment on their long-term survival.

Treatment of cutaneous T-cell lymphoma with combined immunomodulatory therapy: a 14-year experience at a single institution.

To determine the efficacy of multimodality biologic response therapy for patients with cutaneous T-cell lymphoma (CTCL). Retrospective cohort study over a 14-year period. Tertiary care university hospital. A consecutive sample of patients was studied, all 47 of whom carried the clinical and laboratory diagnosis of CTCL: 68% of patients had stage III or IV disease, and 89% had circulating malignant T cells. All 47 patients received photopheresis for 6 or more cycles. Thirty-one patients received treatment with a combination of photopheresis and 1 or more systemic immunostimulatory agents, including interferon alfa, interferon gamma, sargramostim, or systemic retinoids for 3 or more months. Differences in pretreatment prognostic factors, response rates, and survival between patients receiving multimodality therapy and single-modality therapy or historical controls. A total of 79% of patients responded to therapy: 26% had complete remission, and 53% had a partial remission. Median survival from initiation of therapy was 74 months. Median survival for patients with stages III and IV and peripheral blood involvement was 55 months compared with 31 months for historical controls. Compared with the photopheresis monotherapy group, the patients receiving combination immunomodulatory therapy had a worse prognosis at the time of treatment initiation based on multiple prognostic factors. The positive response rates and median survival times were 84% and 74 months, respectively, compared with 75% and 66 months, respectively, for the combination immunomodulatory and photopheresis monotherapy groups (P =.47 for positive response rates and P =.51 for survival). Patients with advanced CTCL and multiple poor prognostic factors who receive treatment with combination immunomodulatory therapy experience higher clinical response rates and longer survival than historical controls. Although the group who received combination therapy had worse prognostic factors at baseline, they had better response rates and overall survival compared with those receiving photopheresis monotherapy.