Patients In Sustained Remission Research Articles

Neutrophil-lymphocyte ratio, pain perception, and disease activity score may serve as important predictive markers for sustained remission in rheumatoid arthritis

The implementation of new treatment strategies based on current recommendations has enabled a greater number of patients with rheumatoid arthritis (RA) to achieve remission. However, there are no definite predictors of sustained remission. Moreover, the absence of clear consensus on the time of withdrawal or reduction of treatment further adds to the treatment burden. This pilot study was intended to evaluate the prognostic potential of various RA-related parameters. All the enrolled subjects (n=124) were clinically evaluated on the basis of various parameters including age, gender, duration of illness before the initiation of disease-modifying anti-rheumatic drugs, tender and swollen joints (28 joints), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), hemoglobin percentage, lymphocyte count, total white-blood cell counts, and neutrophil to lymphocyte ratio (NLR). Student's t-test and discriminant function analysis were performed. The specificity of all parameters and their best possible cut-off to predict relapse were calculated using the receiver operating characteristic (ROC) analysis. A significant difference in terms of pain perception, NLR, tendency to have a significant tender joint count and absolute lymphocyte counts was identified between the patients in sustained remission and those in relapse. The ROC analysis indicated that NLR was consistent in predicting remission. CRP, ESR, and/or disease activity score may not be very effective in differentiating patients with sustainable remission/low disease activity. NLR along with patient's perception of pain may assist in predicting sustained remission.

ADVANCED TREATMENT IN RHEUMATOID ARTHRITIS. IS IT POSSIBLE TO TAPER THE BIOLOGICAL TREATMENT?

Rheumatoid arthritis (RA) is a systemic autoimmune disease, leading to synovial hypertrophy and adjacent bone and cartilage destruction. The combined use of biological agents and methotrexate (MTX) has revolutionised the treatment of RA producing significant improvements in clinical, radiographic and functional outcomes. The results of clinical study and experience of the specialities of rheumatology in clinical statement showed the long treatment may be associated with side effects, in addition biological treatment means high cost. The next goal should be remission without the use of biological agents. That’s why new treatment in RA means the tapering or even stopping the biological treatment in patients with RA who reached remission. In association with the new recommendation EULAR in 2013 there are many studies which showed the possibility of tapering or discontinuing the biological therapy in patients in sustained remission.

Evaluation of the Disease Activity Score in Twenty-Eight Joints-Based Flare Definitions in Rheumatoid Arthritis: Data From a Three-Year Clinical Trial.

ObjectiveTo assess the flare rate using published criteria (Disease Activity Score in 28 joints [DAS28‐2] increase between visits of >1.2 or >0.6 if current DAS28 ≥3.2) in patients receiving constant treatment, and to compare published flare criteria to criteria used by study investigators after biologic treatment discontinuation in the ACT‐RAY study.MethodsPatients with rheumatoid arthritis (n = 553) were randomized to add tocilizumab to ongoing methotrexate, or switch to tocilizumab plus placebo. If DAS28 ≤3.2 occurred at week 24, treatment remained constant until week 52; here we assessed the DAS28‐2 flare rate. Between weeks 52 and 104, patients in sustained remission (DAS28 <2.6 at 2 consecutive visits 12 weeks apart) discontinued tocilizumab and were assessed every 4 weeks. Per protocol, flare was defined as a worsening of disease activity that required treatment beyond the permitted therapy based on investigator opinions (investigator flare) and was compared with the DAS28‐2 definition.ResultsAfter tocilizumab discontinuation, DAS28‐2 was sensitive (88–100%), but not specific (57–65%), for detecting investigator flare. Under constant treatment, DAS28‐2 criteria were met in 136 cases per 100 patient‐years despite stable disease activity. Sustained flares were infrequent. Other DAS28‐based criteria led to similar conclusions.ConclusionDAS28‐based flare occurred more often than investigator‐defined flares after biologic agent discontinuation. More stringent criteria may be more appropriate for clinical practice.

Prevalence and prognostic relevance of cardiac involvement in ANCA-associated vasculitis: Eosinophilic granulomatosis with polyangiitis and granulomatosis with polyangiitis

BackgroundTo investigate the prevalence and prognostic relevance of cardiac involvement in an ANCA-associated vasculitis (AAV) population of eosinophilic granulomatosis with polyangiitis (EGPA) and granulomatosis with polyangiitis (GPA) patients. MethodsProspective cohort study of fifty EGPA and forty-one GPA patients in sustained remission without previous in-depth cardiac screening attending our clinical immunology outpatient department. Cardiac screening included clinical evaluation, ECG, 24-hour Holter registration, echocardiography and cardiac magnetic resonance imaging (CMR) with coronary angiography and endomyocardial biopsy upon indication. Fifty age-, sex- and cardiovascular risk factor-matched control subjects were randomly selected from a population study. Long-term outcome was assessed using all-cause and cardiovascular mortality. ResultsA total of 91 AAV-patients (age 60±11, range 63–87years) were compared to 50-matched control subjects (age 60±9years, range 46–78years). ECG and echocardiography demonstrated cardiac abnormalities in 62% EGPA and 46% GPA patients vs 20% controls (P<0.001 and P=0.014, respectively). A total of 69 AAV-patients underwent additional CMR, slightly increasing the prevalence of cardiac involvement to 66% in EGPA and 61% in GPA patients. After a mean follow-up of 53±18months, presence of cardiac involvement using ECG and echocardiography in AAV-patients showed increased all-cause and cardiovascular mortality (Log-rank P=0.015 and Log-rank P=0.021, respectively). ConclusionCardiac involvement in EGPA and GPA patients with sustained remission is high, even if symptoms are absent and ECG is normal. Moreover, cardiac involvement is a strong predictor of (cardiovascular) mortality. Therefore, risk stratification using cardiac imaging is recommended in all AAV-patients, irrespective of symptoms or ECG abnormalities.

Expression of p-STAT5, c-MYC and IKZF1 By Immunohistochemistry May Differentially Correlate with Clinical Outcome in Adult B- Lymphoblastic Leukemia (B-ALL) According to BCR-ABL Status

Background: Molecular and cytogenetic abnormalities characterize the biologic heterogeneity of B-ALL and provide a strong and independent prognostic factor for treatment outcome. Emerging data highlight the role of tyrosine kinase inhibition (TKI) in those with Philadelphia chromosome positive (Ph+) B-cell acute lymphoblastic leukemia. A new high risk subset, so-called Ph-like ALL, has been recognized, comprising 10-15% of pediatric B-ALL. These cases show similar alterations in IKZF1, and are likely driven by alternative kinase rearrangements, including CRLF2, JAK2, ABL1, and others. Increased STAT5 phosphorylation may broadly classify such patients, and, also suggest a benefit with JAK2 inhibitors or TKI’s. Finally, c-MYC has been recognized as a high risk feature for both B- and T-ALL, though it is unclear whether the risk is similar among Ph+ and Ph- patients in the era of TKI-based therapy.Method and Materials: A retrospective analysis was performed of a series of 75 patients at Moffitt Cancer Center with B-ALL diagnosed between June 2002 and July 2013. Of them, paraffin embedded blocks from patients who had the first diagnostic bone marrow biopsy performed at MCC with a good biopsy quality (> 1.0 cm in length and tumor load over 60% of marrow cellularity) were selected for performing immunohistochemical (IHC) study. Ten normal bone marrows were also included as antibody base-line control. IHC stains were performed according to institutional standard protocol and modified based on the individually purchased antibody. Expression of pSTAT5, c-MYC, and IKZF1 on lymphoblasts was assessed semiquantitatively based on the expression score calculated with staining strength and multiplied by percentage positivity on tumor cells. Clinical outcomes were correlated to the IHC scores. Hazard ratios were generated using standard cox regression analysis. Patient survival was analyzed with Kaplan-Meier method from the date of diagnosis until death from any cause.Results: From 75 total patients, 43 were selected with de novo B-ALL with marrow evaluation at the time of diagnosis and a minimum of 60% blasts on core/clot biopsy. 18 (42%) were Ph+ with median age 52y (18-76), median wbc 14.7 k/uL (0.7-580), and male to female ratio of 1.5. 95% received an intensive induction (HyperCVAD, CALGB8811, ECOG2993, or pediatric regimen), and 94% of Ph+ patients received TKI therapy, either with imatinib (67%) or dasatinib (33%). 35% received an allogeneic transplant in first remission.No significant difference in age, gender, application of intensive therapy, PFS/relapse rate, or OS/death rate. There was trend towards higher wbc (p=0.11) and application of AlloSCT (p=0.11) in the Ph+ group.Using the mean as a cutoff, the IHC staining results showed nuclear expression of pSTAT5 to be more frequently present in Ph+ B-ALL than in Ph- B-ALL (78% vs 32%, p = 0.005), however, no differences in staining were observed with IKZF1 (44% vs 52%, p=0.76), or c-MYC (50% vs 64%, p=0.53). Similar data were generated using absolute staining intensity, with Ph+ B-ALL showing a higher median pSTAT5 score (p<0.001).Neither c-MYC, IKZF1, or pSTAT5 were associated with OS when analyzing the entire cohort. For PFS, only pSTAT5 was significant (p=0.03), with no impact of IKZF1, or c-MYC.Analysis of the Ph- group demonstrated a decrease in PFS (p=.009) and a trend for decreased OS (p=0.125) in those with elevated pSTAT5, possibly identifying this group as ‘ph-like’ ALL. Decreased IKZF1 was not associated with PFS, though, was associated with decreased OS (p=0.031). There was a trend for worse PFS in those with MYC overexpression, with 100% of MYC low patients in sustained remission (p=0.196). This did not translate to an impact on survival, possibly related to treatment related toxicity.Analysis of the Ph+ group demonstrated no impact of pSTAT5, IKZF1, or c-MYC on OS or PFS, suggesting that TKI therapy was able to partially abrogate these risks.Conclusion: Ph+ ALL patients show higher baseline pSTAT5 expression by IHC than Ph- patients. However, those Ph- patients with elevated pSTAT5 show impaired PFS and a trend for worse OS, suggesting that Ph-/pSTAT5 high patients may warrant additional testing to rule out alternative, and potentially actionable, kinase translocations (Ph-like ALL). The impact of low IKZF1 and c-MYC, when assessed by IHC was limited to Ph- patients. DisclosuresShah:Seattle Genetics, Inc.: Research Funding; NCCN: Consultancy; Celgene: Consultancy, Speakers Bureau; SWOG: Consultancy; Pharmacyclics: Consultancy; Janssen: Consultancy. Off Label Use: SGN-CD19A is an investigational agent being studied in patients with B-cell malignancies. SGN-CD19A is not approved for use.

Rapid corticosteroid tapering: Important risk factor for type 1 autoimmune hepatitis relapse in Japan.

Patients with autoimmune hepatitis (AIH) sometimes relapse after immunosuppressive therapies are discontinued or sometimes even while they are still being administrated. Furthermore, relapse often occurs in the absence of AIH relapse risk factors. This study aimed to identify the frequency of relapse and to analyze the risk factors associated with relapse in type 1 AIH patients. Clinical characteristics and therapeutic processes were assessed in 129 type 1 AIH patients. Relapse was identified in 39 (30.2%) type 1 AIH patients after alanine aminotransferase (ALT) level normalization. ALT levels significantly increased when corticosteroid treatment was initiated in relapsed patients compared with that in patients with sustained remission. The reduction dose and rate of corticosteroid taper were significantly increased in relapsed patients compared with those in sustained remission patients. Moreover, positive correlations were identified between the reduction dose/taper rate and initial corticosteroid dose, and ALT levels, total bilirubin levels and hepatitis activity. Multivariate logistic regression analysis identified the corticosteroid reduction rate as significantly associated with AIH relapse. Corticosteroid reduction taper rate until ALT normalization is an important AIH relapse risk factor.

SAT0167 Clinical and Ultrasonographic Evaluation in A Cohort of Sustained Remission Rheumatoid Arthritis Patients after Stopping Biologic Therapy: A Single Center Experience

BackgroundRheumatoid arthritis (RA) patients in clinical remission according to the 2011 ACR/EULAR criteria [1] can develop radiographically revealed hand and foot erosions and joint damage when observed 2-5 years later....

Regulatory and effector T cells changes in remission and resistant state of childhood nephrotic syndrome.

Idiopathic minimal change disease is a disorder of T-cell dysfunction. The relative predominance of regulatory T cells (Tregs), Th1, and Th2 cells in nephrotic syndrome (NS) remains controversial. Imbalance in peripheral blood regulatory and effector T cells (Teff) are linked to cell mediated immune response and may be associated with steroid response in NS. Peripheral blood CD4 + CD25 + FoxP3 + (Tregs), CD4 + IFN-γ+ (Th1), and CD4 + IL-4 + (Th2) lymphocytes were analyzed in 22 steroid-sensitive NS (SSNS) patients in sustained remission, 21 steroid-resistant NS (SRNS) and 14 healthy controls. The absolute percentage values and ratio of Th1/Tregs, Th2/Tregs, and Th1/Th2 were compared between SSNS, SRNS and control subjects. The percentage of Tregs was lower in SRNS patients (P = 0.001) compared with that of SSNS and healthy control. The percentage of Th1 cells was higher in SRNS (P = 0.001) compared to that of SSNS patients; however, it was similar to healthy controls (P = 1.00). The percentage of Th2 cells in SRNS (P = 0.001) was higher as compared to SSNS and controls. The ratio of Th1/Treg cells in SRNS (P = 0.001) was higher as compared to SSNS patients and controls. The ratio of Th2/Treg was also higher in SRNS as compared to SSNS and controls. The ratio of Th1/Th2 cells in SSNS, SRNS, and healthy controls were similar. The cytokines secretion complemented the change in different T-cell subtypes in SSNS, SRNS and healthy controls. However, the IFN-γ secretion in healthy controles was low inspite of similar percentage of Th1 cells among SRNS cases. We conclude that greater ratio of Tregs compared to that Th1 and Th2 favor steroid sensitivity and reverse ratio results in to SRNS. The difference in ratio is related to pathogenesis or it can be used as marker to predict steroid responsiveness needs further evaluation.

Long-term sustained remission in a cohort study of patients with rheumatoid arthritis: choice of remission criteria

ObjectivesRemission is a widely accepted goal for treatment of rheumatoid arthritis (RA) but has to be sustained to arrest joint damage and disability. However, appropriate criteria for the assessment of...

SAT0091 Physical function continues to improve in sustained clinical remission of rheumatoid arthritis (RA)

BackgroundRemission has been proposed as the therapeutic target in RA. Physical function, on the other hand, is one of the major outcomes in RA predicting work disability, health care resource...

SAT0552 Management of Rheumatoid Arthritis in Remission in Current Practice : the 3P Study

BackgroundThe goal of current rheumatoid arthritis management is to achieve remission or low disease activity1. However few studies have been performed on the management of patients in sustained remission, especially...

Association of obesity with worse disease severity in rheumatoid arthritis as well as with comorbidities: A long‐term followup from disease onset

To determine the association of obesity, defined as a body mass index (BMI) ≥30 or ≥28 kg/m(2) or by waist circumference (WC), with disease activity and severity, as well as its relationship to comorbidities in rheumatoid arthritis (RA). The study population comprised 1,596 patients with early RA (mean ± SD age 55.6 ± 14.6 years, 67.8% women) who had been included in the Better Anti-Rheumatic Farmacotherapy observational study from 1992-2006. In 2010, data on lifestyle factors and comorbidities were collected through a postal questionnaire, answered by 1,391 patients. Clinical outcomes were the Disease Activity Score in 28 joints, sustained remission, physical function (Health Assessment Questionnaire [HAQ]), and pain and global health assessed on a visual analog scale, as well as predefined comorbidities. After a mean ± SD of 9.5 ± 3.7 years, the mean ± SD BMI had increased from 25.4 ± 4.2 to 26.0 ± 4.5 kg/m(2) (P = 0.000). The prevalence of BMI ≥30 kg/m(2) was 12.9% at baseline and 15.8% at followup. In multivariable regression, BMI and obesity, defined as a BMI ≥30 or ≥28 kg/m(2) , at both inclusion and the time of the survey were independently associated with higher disease activity, fewer patients in sustained remission, higher HAQ score, more pain, and worse general health. Also, BMI and obesity independently conferred to higher odds for being diagnosed with hypertension, diabetes mellitus, and chronic pulmonary disease. Further, BMI and WC were independently associated with angina pectoris/acute myocardial infarction/coronary revascularization. In contrast, none of the examined obesity variables was associated with the prevalence of stroke or transient ischemic attack. Lifestyle changes during the observational period, such as quitting smoking or diet change, had no impact on the outcomes. Obesity was associated with worse RA disease outcomes and a higher prevalence of comorbidities. Body measurements are recommended to improve prediction of the disease course.

Rapid decrease in adrenal responsiveness to ACTH stimulation after successful pituitary surgery in patients with Cushing’s disease

The aim of this study was to investigate the effects of transsphenoidal surgery (TS) on the adrenal sensitivity to ACTH (adrenocorticotropin) stimulation in patients with Cushing's disease (CD). We measured the cortisol response to 1 μg synthetic ACTH (1-24) 6 days after pituitary surgery in 45 patients with CD. Mean follow-up period was 56·5 months (SE 4·7). In 24 of 28 patients in sustained remission after pituitary surgery, peak cortisol concentrations below 774 nm (28·0 μg/dl) were recorded after stimulation with 1 μg synthetic ACTH (86%). Two patients with recurrent disease after initial remission (late relapse) also showed ACTH-stimulated peak cortisol levels below 774 nM. Fourteen of 15 patients with persistent CD after surgery (early failure) showed absolute peak cortisol levels >774 nm in response to ACTH stimulation. Patients in remission after pituitary surgery for CD showed a rapid decrease of adrenal responsiveness to exogenous ACTH stimulation. This phenomenon may be explained by ACTH-receptor down-regulation in the adrenal cortex after complete removal of the pituitary corticotroph adenoma. In our study, the postoperative low-dose ACTH stimulation test had a sensitivity of 93% and a specificity of 87% in predicting immediate remission of CD after pituitary surgery.

Sustained long‐term remissions with weekly interferon maintenance therapy in hairy cell leukemia

This study evaluates the efficacy of weekly α-interferon (IFN) maintenance therapy in hairy cell leukaemia (HCL), a disease that remains incurable. Nine patients (six male, three female, aged 41-69 yrs) with hairy cell leukaemia (HCL) received IFN 3mU s.c. once weekly as long-term maintenance therapy after achieving optimal clinical and hematological response to initial therapy with thrice weekly IFN. Eight of the nine patients are in a state of sustained response at 3-17 years (median 12 years). Our results are similar to those from three previous studies using long-term IFN maintenance therapy, bringing the total number of patients in sustained remission to 118. We hope these reports will lead to a multi-centre, phase III study of IFN maintenance therapy (including pegylated IFN, given less frequently) in HCL patients achieving optimal response to initial therapy, be it IFN or a purine analogue.

Evaluation of bone mineral density and fat-lean distribution in patients with multiple myeloma in sustained remission.

To study the usefulness of bone mineral density (BMD) in the follow-up of myeloma (MM) patients, BMD was evaluated in 44 MM patients in sustained remission for at least 2 years (35.4 +/- 10.5 months) after high-dose or conventional chemotherapy in a retrospective study. Patients never received bisphosphonates before or during the follow-up. Patients underwent lumbar spine (LS) BMD and a whole body (WB) BMD testing before therapy and at least once in the remission period. At baseline, mean LS BMD was 0.863 +/- 0.026 g/cm2, mean lumbar Z-score was -1.45 SD. LS BMD significantly increased from baseline by 5 +/- 1.8%, 9.3 +/- 1.7%, and 14 +/- 1.9% at 1, 2, and 3 years, respectively. The percentage of patients with a T-score below 2.5 SD decreased from 39% at baseline to 18.5% at 3 years. Compared with baseline, WB BMD decreased by -2.8 +/- 0.5%, -2.6 +/- 0.7%, and -1.7 +/- 0.6% at 1, 2, and 3 years, respectively. Mean percentage change of the fat compartment increased from baseline by +28.4 +/- 7.1% at the trunk, and +17.1 +/- 5% in peripheral areas at 3 years. In conclusion, in MM patients in remission after chemotherapy, LS BMD progressively increased after a mean follow-up of 3 years. These patients never received bisphosphonates, so this increase was related to the anti-myeloma treatment. The major effect on BMD was observed at the LS, which is primarily composed of trabecular bone containing the bone marrow. Interestingly, a drastic increase of the fat content was also observed. These results underlined that BMD and fat-lean evaluation could be of interest in the follow-up of MM patients.

Long-term results of cyclosporine-induced remission of relapsing nephrotic syndrome in children.

Twenty-nine children with nephrotic syndrome were treated with cyclosporine (CsA), 100 mg/m2/day for 6 months and prednisone, 2 mg/kg every other day for 1 month and then subsequently 1 mg/kg every other day for 5 months. A renal biopsy had shown minimal change disease (MCD) in 18 children, focal segmental glomerulosclerosis (FSGS) in 3 children, membranous glomerulonephritis (MGN) in 4 children, membranoproliferative glomerulonephritis (MPGN) in 2 children, and IgA nephropathy in 2 children. All MCD patients went into complete remission during therapy. Five out of 11 steroid-sensitive patients (45.5%) remained in complete remission, while the remaining 6 (54.5%) had 2 to 3 relapses, 19 to 47 months after CsA discontinuation. Two out of 7 steroid-resistant patients (28.6%) were still in complete remission and 5 (71.4%) had 1 to 6 relapses 25 to 49 months after CsA withdrawal. The mean number of relapses in the steroid-sensitive group before and after CsA treatment decreased more (8.5 vs 1.4) than in the steroid-resistant group (8.1 vs 2.4) (p < 0.05). At the most recent examination, 1 of 3 FSGS patients achieved complete remission and 2 had a partial response. Three of 4 MGN patients were in complete remission and 1 was in partial remission. One of 2 MPGN patients achieved complete remission and 1 showed partial remission. Two patients with IgA nephropathy were in partial remission. We compared MCD patients in sustained remission and relapse; the mean CD4/CD8 ratio decreased from 1.5 to 0.9 in the remission group, in comparison with no change in the relapsed group (p < 0.05). The posttreatment renal biopsy showed lesions of nephrotoxicity in 3 of 18 children with MCD whose renal function did not alter after CsA treatment. We concluded: 1) A 6-month treatment of CsA, in combination with a low-dose alternate-day steroid, proved to be effective in maintaining the remission of steroid-sensitive and steroid-resistant MCD patients. 2) The CD4/CD8 ratio can be used as a index to predict remission or relapse after CsA therapy.

ABC of sleep disorders. Impact and epidemiology of sleep disorders.

<h3>Objectives</h3> The treatment target for patients with rheumatoid arthritis (RA) is remission. Imaging techniques and remission criteria may identify patients at risk of flare and associated consequences. This study aimed to determine the clinical, functional and imaging associations of disease flare in patients with RA in remission and any effect on long-term outcomes. <h3>Methods</h3> RA patients in clinical remission as determined by their treating rheumatologist were assessed using clinical, remission criteria, imaging, functional and quality of life measures over 12 months. Flare was defined as any increase in disease activity requiring a change in therapy. <h3>Results</h3> 26% of patients (24/93) in remission experienced a flare within 1 year. Fulfilment of remission criteria was not associated with a reduced likelihood of flare. Increased baseline ultrasound power Doppler (PD) activity (unadjusted OR (95% CI) 4.08 (1.26 to 13.19), p=0.014) and functional disability (Health Assessment Questionnaire Disability Index (HAQ-DI) per 0.1 unit1.27 (1.07 to 1.52), p=0.006) were independently associated with risk of flare. Patients who had a flare had significantly worse long-term clinical (Disease Activity Score 28; mean (95% CI) 2.90 (2.55 to 3.24) vs 2.26 (2.06 to 2.46), p=0.002) and functional outcomes (HAQ-DI; 0.412 (0.344 to 0.481) vs 0.322 (0.282 to 0.362), p=0.029) at 12 months compared with patients in sustained remission. <h3>Conclusion</h3> The presence of PD activity was the most accurate determinant of flare in RA patients in remission. Flare was associated with worse clinical and functional outcomes. These results suggest ultrasound could form an important part of remission assessment in RA.

Sequential evaluation of cutaneous delayed hypersensitivity responses to recall and to lymphoid cell line antigens in Burkitt's lymphoma.

Delayed cutaneous hypersensitivity reactions to standard recall antigens (candidin, mumps and PPD), to crude membrane extracts of a cell line derived from Burkitt's lymphoma (Raji) and to cell line derived from normal lymphocytes (F265) were sequentially evaluated in 44 patients with Burkitt's lymphoma. Sixteen patients (36%) manifested delayed hypersensitivity responses to the standard antigens and seven (16%) to the Raji membrane extract at presentation. Following successful chemotherapy, there was prompt and significant improvement of reactivity to both the standard and Raji antigens (p greater than 0.001), suggesting that the initial impairment of delayed hypersensitivity was most likely related to tumor burden. By 9 months after treatment, all patients in sustained remission expressed reactivity to Raji and 21 of 22 to the standard antigens. None of the patients skin-tested with the F265 extract at presentation gave a positive response and only one subsequently expressed reactivity after remission was induced. On relapse, reactivity to the standard antigens was more readily lost (4 of 11) then reactivity to the Raji extract (1 of 7). Pretreatment delayed hypersensitivity to the standard antigens also correlated better with long-term survival than to pretreatment responses to Raji. It remains to be determined whether the antigens expressed in the Raji extract are indeed tumor-specific or related to Epstein-Barr virus.