Autologous stem cell transplantation for untreated transformed indolent B-cell lymphoma in first remission: an international, multi-centre propensity-score-matched study.

High-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) are used as consolidation in first remission (CR1) in some centres for untreated, transformed indolent B-cell lymphoma (Tr-iNHL) but the evidence base is weak. A total of 319 patients with untreated Tr-iNHL meeting prespecified transplant eligibility criteria [age <75, LVEF ≥45%, no severe lung disease, CR by positron emission tomography or computed tomography ≥3 months after at least standard cyclophosphamide, doxorubicin, vincristine and prednisolone with rituximab (R-CHOP) intensity front-line chemotherapy] were retrospectively identified. Non-diffuse large B-cell lymphoma transformations were excluded. About 283 (89%) patients had follicular lymphoma, 30 (9%) marginal-zone lymphoma and six (2%) other subtypes. Forty-nine patients underwent HDC/ASCT in CR1, and a 1:2 propensity-score-matched cohort of 98 patients based on age, stage and high-grade B-cell lymphoma with MYC, BCL2 and/or BCL6 rearrangements (HGBL-DH) was generated. After a median follow-up of 3·7 (range 0·1-18·3) years, ASCT was associated with significantly superior progression-free survival [hazard ratio (HR) 0·51, 0·27-0·98; P = 0·043] with a trend towards inferior overall survival (OS; HR 2·36;0·87-6·42; P = 0·1) due to more deaths from progressive disease (8% vs. 4%). Forty (41%) patients experienced relapse in the non-ASCT cohort - 15 underwent HDC/ASCT with seven (47%) ongoing complete remission (CR); 10 chimeric antigen receptor-modified T-cell (CAR-T) therapy with 6 (60%) ongoing CR; 3 allogeneic SCT with 2 (67%) ongoing CR. Although ASCT in CR1 improves initial duration of disease control in untreated Tr-iNHL, the impact on OS is less clear with effective salvage therapies in this era of CAR-T.

Adjuvant everolimus in high-risk diffuse large B-cell lymphoma: final results from the PILLAR-2 randomized phase III trial.

Background: Patients with diffuse large B-cell lymphoma (DLBCL) with an International Prognostic Index (IPI) ≥3 are at higher risk for relapse after a complete response (CR) to first-line rituximab-based chemotherapy (R-chemo). Everolimus has single-agent activity in lymphoma. PILLAR-2 aimed to improve disease-free survival (DFS) with 1 year of adjuvant everolimus. Patients and methods: Patients with high-risk (IPI ≥3) DLBCL and a positron emission tomography/computed tomography-confirmed CR to first-line R-chemo were randomized to 1 year of everolimus 10 mg/day or placebo. The primary end point was DFS; secondary end points were overall survival, lymphoma-specific survival, and safety. Results: Between August 2009 and December 2013, 742 patients were randomized to everolimus (n = 372) or placebo (n = 370). Median follow-up was 50.4 months (range 24.0-76.9). Overall, 47% of patients were ≥65 years, 50% were male, and 42% had an IPI of 4 or 5. 48% and 67% completed everolimus and placebo, respectively. Primary reasons for everolimus discontinuation versus placebo were adverse events (AEs; 30% versus 12%) and relapsed disease (6% versus 13%). Everolimus did not significantly improve DFS compared with placebo (hazard ratio 0.92; 95% CI 0.69-1.22; P = 0.276). Two-year DFS rate was 77.8% (95% CI 72.7-82.1) with everolimus and 77.0% (95% CI 72.1-81.1) with placebo. Common grade 3/4 AEs with everolimus were neutropenia, stomatitis, and decreased CD4 lymphocytes. Conclusions: Adjuvant everolimus did not improve DFS in patients already in PET/CT-confirmed CR. Future approaches should incorporate targeted agents such as everolimus with R-CHOP rather than as adjuvant therapy after CR has been obtained. ClinicalTrials.gov: NCT00790036.

Characterization of indeterminate soft tissue masses referred for biopsy: What is the added value of contrast imaging at 3.0 tesla?

PURPOSE: To assess the added value of contrast-enhanced (CE) MR sequences (static CE-MR sequences, dynamic CE-MR sequences) to noncontrast enhanced MR sequences (non-CE-MR sequences) including T1, fluid-sensitive, and diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) mapping for characterizing "indeterminate" soft tissue masses (STMs) as benign or malignant. MATERIALS AND METHODS: Thirty-nine patients with indeterminate STMs (27 benign, 12 malignant) underwent 3 Tesla MRI with conventional non-CE-MR sequences (T1-weighted, fluid-sensitive), DWI (b-values 50, 400, 800, ADC mapping), dynamic CE-MR sequences (7-s time resolution), and static CE-MR sequences. Two readers independently reviewed imaging in four sessions (conventional non-CE-MR sequences alone, conventional+DWI/ADC, conventional+DWI/ADC+static CE-MR sequences, conventional+DWI/ADC+static CE-MR sequences dynamic CE-MR sequences). Readers recorded the potential of malignancy at each session; reader diagnostic performance (receiver operating characteristics analysis) and inter-observer variability (weighted kappa [k]) were determined. RESULTS: Diagnostic performance for distinguishing benign and malignant STMs was highest with the addition of dynamic CE-MR sequences (reader 1, area under the curve [AUC] 0.91; reader 2, AUC 0.88). The diagnostic performance of static CE-MR sequences (reader 1, AUC 0.86; reader 2, AUC 0.84) was not superior to non-CE-MR sequences with DWI (reader 1, AUC 0.88; reader 2, AUC 0.8). Interobserver agreement was: k = 0.82 (static CE-MRI), k = 0.79 (dynamic CE-MRI), k = 0.53 (non-CE-MR sequences without DWI), and k = 0.63 (with DWI). CONCLUSION: Non-CE-MR sequences offer similar diagnostic performance to imaging with the addition of static CE-MR sequences, but their interobserver reliability is lower. The addition of dynamic CE-MR sequences offers the higher diagnostic performance for distinguishing benign and malignant indeterminate STMs. LEVEL OF EVIDENCE: 3 J. Magn. Reson. Imaging 2017;45:390-400.

MDCT of hand and wrist infections: emphasis on compartmental anatomy.

Hand and wrist infections can present with a spectrum of manifestations ranging from cellulitis to deep-space collections. The various infectious processes can be categorised as superficial or deep infections based on their respective locations relative to the tendons. Superficial hand infections are located superficial to the tendons and are comprised of cellulitis, lymphangitis, paronychia, pulp-space infections, herpetic whitlow, and include volar as well as dorsal subcutaneous abscesses. Deep hand infections are located deep to the tendon sheaths and include synovial space infections, such as infectious tenosynovitis, deep fascial space infections, septic arthritis, necrotising fasciitis, and osteomyelitis. Knowledge of hand and wrist compartmental anatomy is essential for the accurate diagnosis and management of hand infections. Although early and superficial infections of the hand may respond to non-surgical management, most hand infections are surgical emergencies. Multidetector computed tomography (MDCT), with its muliplanar reformation (MPR) and three-dimensional (3D) capabilities, is a powerful tool in the emergency setting for the evaluation of acute hand and wrist pathology. The clinical and imaging features of hand and wrist infections as evident on MDCT will be reviewed with emphasis on contiguous and closed synovial and deep fascial spaces. Knowledge of hand compartmental anatomy enables accurate characterisation of the infectious process and localise the extent of disease in the acute setting.

MRI characteristics associated with high-grade myxoid liposarcoma.

AIM: To identify magnetic resonance imaging (MRI) features differentiating high-grade (>5% round-cell component) from low-grade myxoid liposarcomas (LPS) (≤5% round-cell component). MATERIALS AND METHODS: Informed consent was waived. Patients with myxoid LPS and MRI before biopsy, neoadjuvant therapy, and surgery were included retrospectively. High-grade components were recorded from histological specimens by a pathologist (24 years of experience). Images were evaluated by a senior radiologist (>12 years of experience) for tumour size, location, tissue layer, and MRI features (signal intensity, heterogeneity, margin, and perilesional characteristics). Descriptive statistics, Fisher's exact test to identify associations with a round-cell component, and multivariate logistic regression to identify independent predictors of high-grade tumours were used. RESULTS: Thirty-one patients (16 women [mean 51.1 years; range 19-79 years] and 15 men [mean 45.5 years; range 18-95 years]) with myxoid LPS (23 low-grade, eight high-grade) were included. All high-grade lesions had lipid signal, a peritumoural capsule and peritumoural contrast enhancement, and more commonly exhibited heterogeneous signal; however, the average size of ≥10 cm was the strongest independent indicator of high-grade status (odds ratio [OR], 14.6; 95% confidence interval [CI]: 1.6, 131). CONCLUSION: Size ≥10 cm is most strongly associated with high-grade myxoid LPS (round-cell component >5%). Other features possibly differentiating high-grade from low-grade status include lesion margin, lipid signal, and perilesional characteristics.

Patients with classical Hodgkin lymphoma experiencing disease progression after treatment with brentuximab vedotin have poor outcomes.

BACKGROUND: Brentuximab vedotin (BV) is a key therapeutic agent for patients with relapsed/refractory classical Hodgkin lymphoma (cHL). The outcomes of patients experiencing disease progression after BV are poorly described. PATIENTS AND METHODS: We reviewed our institutional database to identify patients with cHL treated with BV who were either refractory to treatment or experienced disease relapse. We collected clinicopathologic features, treatment details at progression and outcome. RESULTS: One hundred patients met inclusion criteria, with a median age of 32 years (range 18-84) at progression after BV. The median number of treatments before BV was 3 (range 0-9); 71 had prior autologous stem cell transplant. The overall response rate (ORR) to BV was 57%, and the median duration of BV therapy was 3 months (range 1-25). After disease progression post-BV, the most common treatment strategies were investigational agents (n = 30), gemcitabine (n = 15) and bendamustine (n = 12). The cumulative ORR to therapy was 33% (complete response 15%). After a median follow-up of 25 months (range 1-74), the median progression-free (PFS) and overall survival (OS) were 3.5 and 25.2 months, respectively. In multivariate analysis, no factors analyzed were predictive of PFS; age at progression >45 years and serum albumin <40 g/l at disease progression were associated with increased risk of death. Among patients who achieved response to therapy, allogeneic stem cell transplantation was associated with a non-significant trend toward superior OS (P = 0.11). CONCLUSIONS: Patients with BV-resistant cHL have poor outcomes. These data serve as a reference for newer agents active in BV-resistant disease.

Factors influencing outcome in advanced stage, low-grade follicular lymphoma treated at MD Anderson Cancer Center in the rituximab era.

BACKGROUND: The optimal initial therapy of follicular lymphoma (FL) remains unclear. The aims of this study were to compare primary treatment strategies and assess the impact of maintenance rituximab and patterns of treatment failure. PATIENTS AND METHODS: We retrospectively analyzed patients with treatment-naive advanced stage, grade 1-2 FL treated at our center from 2004 to 2014. We included 356 patients treated on clinical trials or standard of care with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP, n = 119); R-CHOP with maintenance (R-CHOP + M, n = 65); bendamustine/rituximab (BR, n = 45); BR with maintenance (BR + M, n = 35); R(2) (n = 94). We compared baseline characteristics, progression-free survival (PFS), overall survival (OS) and analyzed prognostic factors using univariate and multivariate analysis adjusted for treatment. RESULTS: After a median follow-up of 4 years (range 0.2-15.0), the 3-year PFS was 60% [95% confidence interval (CI) 51% to 69%] for R-CHOP, 72% (59% to 82%) for R-CHOP + M, 63% (42% to 78%) for BR, 97% (80% to 100%) for BR + M and 87% (78% to 93%) for R(2). Patients treated with R-chemotherapy had more high-risk features than patients treated with R(2) but, by adjusted multivariate analysis, treatment with R(2) [hazard ratio (HR) 0.39 (0.17-0.89), P = 0.02] was associated with a superior PFS. Eastern Cooperative Oncology Group Performance status of one or more predicted inferior OS. Among patients treated with R-chemotherapy, maintenance was associated with the superior PFS [HR 0.38 (95% CI 0.21-0.68)]. By adjusted multivariate analysis, disease progression within 2 years [HR 5.1 (95% CI 1.57-16.83)] and histologic transformation (HT) [HR 11.05 (95% CI 2.84-42.93)] increased risk of death. CONCLUSION: Induction therapy with R(2) may result in disease control which is comparable with R-chemotherapy. Early disease progression and HT are predictive of inferior survival.

Assessing vascular effects of adding bevacizumab to neoadjuvant chemotherapy in osteosarcoma using DCE-MRI.

BACKGROUND: The purpose of this study was to assess the impact of bevacizumab alone and in combination with cytotoxic therapy on tumour vasculature in osteosarcoma (OS) using DCE-MRI. METHODS: Six DCE-MRI and three (18)F-FDG PET examinations were scheduled in 42 subjects with newly diagnosed OS to monitor the response to antiangiogenic therapy alone and in combination with cytotoxic therapy before definitive surgery (week 10). Serial DCE-MRI parameters (K(trans), v(p), and v(e)) were examined for correlation with FDG-PET (SUV(max)) and association with drug exposure, and evaluated with clinical outcome. RESULTS: K(trans) (P=0.041) and v(p) (P=0.001) significantly dropped from baseline at 24 h after the first dose of bevacizumab alone, but returned to baseline by 72 h. Greater exposure to bevacizumab was correlated with larger decreases in v(p) at day 5 (P=0.04) and week 10 (P=0.02). A lower K(trans) at week 10 was associated with greater percent necrosis (P=0.024) and longer event-free survival (P=0.034). CONCLUSIONS: This is the first study to demonstrate significant changes of the plasma volume fraction and vascular leakage in OS with bevacizumab alone. The combination of demonstrated associations between drug exposure and imaging metrics, and imaging metrics and patient survival during neoadjuvant therapy, provides a compelling rationale for larger studies using DCE-MRI to assess vascular effects of therapy in OS.

Association of mucoid degeneration of anterior cruciate ligament with knee meniscal and cartilage damage.

OBJECTIVE: To assess the prevalence of anterior cruciate ligament (ACL) mucoid degeneration in patients referred for routine knee magnetic resonance (MR) imaging, and its association with age and structural joint damage. METHOD: Four independent radiologists assessed 413 consecutive knee MR examinations for the presence of a normal or ruptured ACL, or ACL mucoid degeneration. Knees with ACL mucoid degeneration were frequency matched by age, sex, and MR field strength with consecutive control knees with a normal ACL (1:2 ratio). Differences in meniscal and cartilage damage of the tibiofemoral compartments, as determined by the Whole-Organ MR Imaging Score (WORMS) system, were compared by Mann-Whitney U tests. Multivariable logistic regression analysis identified the association of ACL mucoid degeneration with severe MTFC cartilage damage (WORMS≥5). RESULTS: Patients with ACL mucoid degeneration (n = 36; 36% males; median age 55.5 years, range: 26-81) were older than patients with a normal (P < 0.001) or ruptured ACL (P < 0.001), without sex predilection (P = 0.76), and were more frequently diagnosed at 3 T (12%) compared to 1.5 T (2%). Knees with ACL mucoid degeneration had statistically significantly more medial meniscal (P < 0.001) and central and posterior medial tibiofemoral compartment (MTFC) cartilage (P < 0.001) damage compared with control knees (n = 72), but there were no differences in patients ≤50 years (P = 0.09 and 0.32, respectively). In multivariable logistic regression, severe MTFC cartilage damage (WORMS≥5) was significantly associated with ACL mucoid degeneration (odds ratio 4.09, 95% confidence interval 1.29-12.94, P = 0.016). CONCLUSION: There is a strong association between ACL mucoid degeneration and cartilage damage in the central and posterior MTFC, especially in patients >50 years.

Assessment of image quality in soft tissue and bone visualization tasks for a dedicated extremity cone-beam CT system.

OBJECTIVE: To assess visualization tasks using cone-beam CT (CBCT) compared to multi-detector CT (MDCT) for musculoskeletal extremity imaging. METHODS: Ten cadaveric hands and ten knees were examined using a dedicated CBCT prototype and a clinical multi-detector CT using nominal protocols (80 kVp-108mAs for CBCT; 120 kVp- 300 mAs for MDCT). Soft tissue and bone visualization tasks were assessed by four radiologists using five-point satisfaction (for CBCT and MDCT individually) and five-point preference (side-by-side CBCT versus MDCT image quality comparison) rating tests. Ratings were analyzed using Kruskal-Wallis and Wilcoxon signed-rank tests, and observer agreement was assessed using the Kappa-statistic. RESULTS: Knee CBCT images were rated "excellent" or "good" (median scores 5 and 4) for "bone" and "soft tissue" visualization tasks. Hand CBCT images were rated "excellent" or "adequate" (median scores 5 and 3) for "bone" and "soft tissue" visualization tasks. Preference tests rated CBCT equivalent or superior to MDCT for bone visualization and favoured the MDCT for soft tissue visualization tasks. Intraobserver agreement for CBCT satisfaction tests was fair to almost perfect (κ ~ 0.26-0.92), and interobserver agreement was fair to moderate (κ ~ 0.27-0.54). CONCLUSION: CBCT provided excellent image quality for bone visualization and adequate image quality for soft tissue visualization tasks. KEY POINTS: • CBCT provided adequate image quality for diagnostic tasks in extremity imaging. • CBCT images were "excellent" for "bone" and "good/adequate" for "soft tissue" visualization tasks. • CBCT image quality was equivalent/superior to MDCT for bone visualization tasks.

Glenoid notch MRI findings do not predict normal variants of the anterior and superior labrum.

AIM: To determine (1) the relationship of a glenoid notch to the presence of a normal labral variant in the anterior-superior glenoid labrum; (2) the inter- and intra-observer reliability of recognising a glenoid notch; and (3) whether magnetic resonance arthrography (MRA) is more reliable than non-contrast magnetic resonance imaging (MRI) in visualising a glenoid notch. MATERIALS AND METHODS: From 1995 through 2010, 104 patients underwent MRI or MRA before diagnostic shoulder arthroscopy by the senior author. Five blinded musculoskeletal radiologists independently read the images twice to evaluate for the presence or absence of a glenoid notch. Fifty-nine (57%) patients had normal anterior-superior labral variants. The authors calculated the relationship of the readings to the arthroscopically determined presence or absence of a normal labral variant and the reading's diagnostic performance and rater reliability. RESULTS: On average, 38% (range 9-65%) of the glenoid scans were read as notched. The sensitivity, specificity, positive predictive value, and negative predictive value of the notch relative to the presence of a normal variant were 43.1%, 71.2%, 70.2%, and 48% versus 44.3%, 77.5%, 79.4%, and 56.1% for MRI and MRA, respectively. The overall average intra-observer κ-values were 0.438 (range 0.203-0.555) and 0.346 (range -0.102 to 0.570) for MRI and MRA, respectively. The average interobserver intra-class correlation coefficient reliability values were 0.730 (range 0.693-0.760) and 0.614 (range 0.566-0.662) for MRI and MRA, respectively. CONCLUSIONS: A notched glenoid on MRI lacks sufficient diagnostic performance and rater reliability for the clinical detection and prediction of normal anterior-superior labral variants.

Gradient-echo in-phase and opposed-phase chemical shift imaging: role in evaluating bone marrow.

Chemical shift imaging (CSI) provides valuable information for assessing the bone marrow, while adding little to total examination time. In this article, we review the uses of CSI for evaluating bone marrow abnormalities. CSI can be used for differentiating marrow-replacing lesions from a range of non-marrow-replacing processes, although the sequence is associated with technical limitations and pitfalls. Particularly at 3 T, susceptibility artefacts are prevalent, and optimal technical parameters must be implemented with appropriate choices for echo times.

Chemical shift imaging at 3 Tesla: effect of echo time on assessing bone marrow abnormalities.

OBJECTIVE: Our purpose is to test the effect of varied in-phase (IP) and opposed-phase (OP) sequence order on characterizing marrow signal changes at 3T. MATERIALS AND METHODS: The study was HIPAA compliant and IRB approved. Informed consent was waived. At 3T, IP and OP sequences were acquired in three patients with biopsy-proven osteosarcomas, using two methods: approach 1 (OP acquisition before IP acquisition) and approach 2 (OP after IP). Signal intensity (SI) measurements in 12 locations of biopsy-proven osteosarcoma and in six locations with normal bone marrow were performed independently by two experienced musculoskeletal radiologists. The signal intensity ratio (SIR) was measured within the marrow where there was T1 signal lower than skeletal muscle. A SIR < 20 % on the OP compared with IP imaging was considered positive for marrow replacement, while SIR > = 20 % was considered negative. Interobserver agreement was measured by the Lin concordance correlation coefficient (CCC). RESULTS: In 75 % (18/24) of locations within the biopsy-proven tumors, the SIR was >20 % (SI drop more than 20 % in OP compared to IP) using approach 2 and in 100 % (24/24) of the locations the SIR was <20 % (SI drop less than 20 % in OP compared to IP) using approach 1, indicating a high percentage of false-negative results by approach 2, and no false-negative results with approach 1. There was good agreement between observer measurement (CCC = 0.96). CONCLUSIONS: At 3T, the OP sequence should be acquired prior to the IP sequence, because susceptibility artifacts on a later-acquired OP sequence may lead to an erroneous interpretation of marrow signal abnormalities.

A randomized trial of a single-dose rasburicase versus five-daily doses in patients at risk for tumor lysis syndrome.

BACKGROUND: Tumor lysis syndrome (TLS) is a life-threatening disorder characterized by hyperuricemia and metabolic derangements. The efficacy of rasburicase, administered daily for 5 days, has been well established. However, the optimal duration of therapy is unknown in adults. PATIENTS AND METHODS: We evaluated the efficacy of rasburicase (0.15 mg/kg) administered as single dose followed by as needed dosing (maximum five doses) versus daily dosing for 5 days in adult patients at risk for TLS. RESULTS: Eighty of the 82 patients enrolled received rasburicase; 40 high risk [median uric acid (UA) 8.5 mg/dl; range, 1.5-19.7] and 40 potential risk (UA = 5.6 mg/dl; range, 2.4-7.4). Seventy-nine patients (99%) experienced normalization in their UA within 4 h after the first dose; 84% to an undetectable level (<0.7 mg/dl). Thirty-nine of 40 (98%) patients in the daily-dose arm and 34 of 40 (85%) patients in single-dose arm showed sustained UA response. Six high-risk patients within the single-dose arm required second dose for UA >7.5 mg/dl. Rasburicase was well tolerated; one patient with glucose-6-phosphate dehydrogenase deficiency developed methemoglobinemia and hemolysis. CONCLUSIONS: Rasburicase is highly effective for prevention and management of hyperuricemia in adults at risk for TLS. Single-dose rasburicase was effective in most patients; only a subset of high-risk patients required a second dose.

Prospective trial of targeted radioimmunotherapy with Y-90 ibritumomab tiuxetan (Zevalin) for front-line treatment of early-stage extranodal indolent ocular adnexal lymphoma.

BACKGROUND: To determine the efficacy and side-effects of (90)Y ibritumomab tiuxetan (Zevalin) as front-line treatment in patients with early-stage extranodal indolent lymphoma of the ocular adnexa (orbit, conjunctiva, or eyelid). PATIENTS AND METHODS: From August 2004 to November 2007, 12 patients with stages I-E extranodal indolent lymphoma of the ocular adnexa were enrolled in a prospective trial of rituximab followed by (90)Y ibritumomab tiuxetan (Zevalin therapeutic regimen). For each patient, clinical examinations and imaging studies were used to document response to therapy using the The International Working Group response criteria. All patients had (111)In ibritumomab tixuetan imaging to confirm expected biodistribution before (90)Y-Zevalin therapy; in addition, three patients had an optional single photon emission computed tomography-computed tomography scan to estimate the absorbed radiation dose to the orbital and ocular tissues. RESULTS: The study included seven women and five men. The median age was 60 years (range 22-79). Nine patients had mucosa-associated lymphoid tissue lymphoma of conjunctiva or orbit; three patients had grades 1-2 follicular lymphoma of orbit. One patient who had been deemed stage I-E initially was found to have another lesion in her deltoid muscle on positron emission tomography 2 weeks after enrollment. She was kept on trial although her disease was reclassified as stage IV due to this single additional (biopsy-proven) site. Ten patients had a complete response and two partial response (PR) within 3 months of treatment. One patient had a recurrence in the upper eyelid 6 months after an initial PR; he then received 30 Gy of external-beam radiotherapy (EBRT). His disease later progressed again in the orbit and he is currently being considered for other treatments. A second patient who attained a PR has remained stable with no progression 12 months after treatment. With a median follow-up time of 20 months (range 6-44 months), there were no cases of distant (extraorbital) relapse. All 12 patients experienced grade I or II transient pancytopenia during the first 3 months after enrollment in the trial. There were no episodes of grade III or IV myelosuppression. The estimated absorbed radiation dose to the orbital soft tissues was <3 Gy, 10 times lower than that with EBRT. CONCLUSIONS: Rituximab followed by (90)Y ibritumomab tiuxetan is an effective and safe front-line treatment for early-stage extranodal indolent B-cell lymphoma of the ocular adnexa.

The addition of rituximab to CHOP chemotherapy improves overall and failure-free survival for follicular grade 3 lymphoma.

BACKGROUND: The benefit of adding rituximab to anthracycline-based therapy for follicular lymphoma grade 3 has not been studied. PATIENTS AND METHODS: We retrospectively reviewed the records of 45 patients with follicular grade 3 lymphoma who were treated with rituximab and the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) at The University of Texas MD Anderson Cancer Center. Response rate, failure-free survival (FFS), and overall survival (OS) were estimated and a historical comparison to CHOP-only-treated patients was made. RESULTS: The International Prognostic Index (IPI) distribution was 47% low, 36% low intermediate, 13% high intermediate, and 4% high risk. The complete response rate was 96%. Forty-four of 45 patients are still alive. Median follow-up for the alive patients is 3.5 years. The 3-year FFS rate according to the IPI was 80% [95% confidence interval (CI) 64% to 100%] in low, 81% in low intermediate (95% CI 64% to 100%), and 50% (95% CI 25% to 100%) in high-intermediate/high-risk patient group. The addition of rituximab to CHOP improved both 5-year FFS, 71% (95% CI 58% to 87%) compared with 44% (95% CI 36% to 55%) with P value of 0.019, and 5-year OS, 98% (95% CI 93% to 100%) compared with 75% (95% CI 67% to 84%) with P value of 0.0034. CONCLUSION: The addition of rituximab to CHOP provided a high response rate and excellent early survival. Poor-risk patients continue to demonstrate a high rate of failure despite the use of rituximab.

Concordant bone marrow involvement of diffuse large B-cell lymphoma represents a distinct clinical and biological entity in the era of immunotherapy.

In diffuse large B-cell lymphoma (DLBCL), the clinical and biological significance of concordant and discordant bone marrow (BM) involvement have not been well investigated. We evaluated 712 de novo DLBCL patients with front-line rituximab-containing treatment, including 263 patients with positive and 449 with negative BM status. Compared with negative BM disease, concordant BM adversely impacted overall and progression-free survival, independent of the International Prognostic Index (IPI) and cell-of-origin classification. Once BM is concordantly involved, poor prognosis was not associated with the extent of BM involvement. Conversely, patients with discordant BM showed favorable overall survival similar to stage I-II DLBCL. A BM-adjusted IPI, using three parameters: concordant BM involvement, age >60 years, and performance status >1, improves the risk stratification for DLBCL with positive BM. Intensive immunochemotherapy seemingly rendered survival benefit for patients with concordant BM, as did rituximab maintenance for the discordant BM group. Frequently revealing adverse clinical and molecular characteristics, patients with concordant BM demonstrated gene expression signatures relevant to tumor cell proliferation, migration and immune escape. In conclusion, clinical and biological heterogeneity is seen in DLBCL with positive BM but concordant BM involvement represents a distinct subset with unfavorable gene signatures, high-risk clinicopathologic features and poor prognosis.

A phase I/II trial of pixantrone (BBR2778), methylprednisolone, cisplatin, and cytosine arabinoside (PSHAP) in relapsed/refractory aggressive non-Hodgkin's lymphoma.

The purpose of the study was to evaluate the safety, efficacy, and pharmacokinetics of pixantrone (BBR2778) when substituted for etoposide in the ESHAP regimen in patients with aggressive relapsed or refractory non-Hodgkin's lymphoma. Nineteen patients received protocol therapy, consisting of pixantrone 80 mg/m2 over 1 h on day 1, methylprednisolone 500 mg on days 1 - 5, cisplatin 25 mg/m2 on days 1 - 4, and cytarabine 2000 mg/m2 on day 5. Cycles were repeated every 21 days, in the outpatient setting. Dose limiting toxicity, consisting of bone marrow suppression, occurred at the first dose level (80 mg/m2), which was defined as the recommended dose. Grade 3 and 4 toxicities were mainly hematologic. Only one patient had grade 4 febrile neutropenia. No significant decreases in ejection fraction greater than 20% occurred. Overall response rate was 58%, with 37% complete and 21% partial responses. Six of the 11 responders (55%) underwent stem cell transplant. Median time to progression and overall median survival were 5.7 months and 14.5 months, respectively. There is no significant interaction between pixantrone and the combined drugs. The recommended dose of pixantrone in combination with methylprednisolone, cytarabine, and cisplatin (PSHAP) is 80 mg/m2. PSHAP is an active salvage regimen and should be further evaluated as a pretransplant cytoreductive regimen.

Reduced-intensity allogeneic stem cell transplantation in relapsed and refractory Hodgkin's disease: low transplant-related mortality and impact of intensity of conditioning regimen.

A total of 40 patients with relapsed/refractory Hodgkin's disease (HD) underwent reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (allo-SCT) from an HLA-identical sibling (n=20) or a matched unrelated donor (n=20). The median age was 31 years (range 18-58). Disease status at allo-SCT was refractory relapse (n=14) or sensitive relapse (n=26). The conditioning regimens were fludarabine-cyclophosphamide+/-antithymocyte globulin (n=14), a less intensive regimen, and fludarabine-melphalan (FM) (n=26), a more intensive one. The two groups had similar prognostic factors. The median time to neutrophil recovery (ie absolute neutrophil count >/=500/microl) was 12 days (range 10-24). The median time to platelet recovery (ie platelet count >/=20 000/microl) was 17 days (range 7-132). Day 100 and cumulative (18-month) transplant-related mortalities (TRMs) were 5 and 22%. Twenty-four patients (60%) are alive (14 in complete remission or complete remission, unconfirmed/uncertain) with a median follow-up of 13 months (4-78). In all, 16 patients expired (TRM n=8, disease progression n=8). FM patients had better overall survival (73 vs 39% at 18 months; P=0.03), and a trend towards better progression-free survival (37 vs 21% at 18 months; P=0.2). RIC allo-SCT is feasible in relapsed/refractory HD patients with a low TRM. The intensity of the preparative regimen affects survival.