Local radiotherapy and measurable residual disease-driven immunotherapy in patients with early-stage follicular lymphoma (FIL MIRO): final results of a prospective, multicentre, phase 2 trial.

BACKGROUND: The mainstay of treatment for early-stage follicular lymphoma is local radiotherapy, with a possible role for anti-CD20 monoclonal antibody (mAb). We aimed to evaluate the effect of these treatments using a measurable residual disease (MRD)-driven approach. METHODS: This prospective, multicentre, phase 2 trial was conducted at 27 centres of the Fondazione Italiana Linfomi (FIL) in Italy. Eligible participants were adults (≥18 years) with newly diagnosed, histologically confirmed follicular lymphoma (stage I or II; grade I-IIIa). Patients were initially treated with 24 Gy involved-field radiotherapy over 12 days; those who were MRD-positive after radiotherapy or during follow-up received eight intravenous doses (1000 mg per dose; one dose per week) of the anti-CD20 mAb ofatumumab. The primary endpoint was the proportion of patients who were MRD-positive after involved-field radiotherapy and became MRD-negative after ofatumumab treatment. Patients were included in the primary endpoint analysis population if they were positive for BCL2::IGH rearrangement at enrolment in peripheral blood or bone marrow samples. MRD positivity was defined as the persistence of BCL2::IGH rearrangement in peripheral blood or bone marrow, assessed centrally by laboratories of the FIL MRD Network. The trial was registered with EudraCT, 2012-001676-11. FINDINGS: Between May 2, 2015, and June 1, 2018, we enrolled 110 participants, of whom 106 (96%) were eligible and received involved-field radiotherapy. Of these, 105 (99%) were White, one (1%) was Black, 50 (47%) were male, and 56 (53%) were female. Of 105 participants in whom BCL2::IGH status was evaluable, 32 (30%) had a detectable BCL2::IGH rearrangement at baseline. After radiotherapy, 12 (40%) of 30 patients reached MRD-negative status, which was long-lasting (at least 36 or 42 months) in three (25%). In those who were MRD-positive after radiotherapy, ofatumumab induced MRD-negativity in 23 (92%; 95% CI 74-99) of 25 evaluable patients. After a median follow-up of 46·1 months (IQR 42·8-50·8), 14 (61%) of these 23 patients remain in complete response and are MRD-negative. The most common grade 3-4 adverse events were infusion-related reactions, observed in four patients. INTERPRETATION: Local radiotherapy is frequently not associated with the eradication of follicular lymphoma. An MRD-driven, anti-CD20 monoclonal antibody consolidation enables molecular remission to be reached in almost all patients and is associated with a reduced incidence of relapse over time. A clinical advantage of an MRD-driven consolidation is therefore suggested. FUNDING: AIRC Foundation for Cancer Research in Italy, Novartis International, and GlaxoSmithKline.

End of induction [18F]FDG PET is prognostic for progression-free survival and overall survival in follicular lymphoma patients enrolled in the FOLL12 trial.

PURPOSE: To evaluate the reliability of the Deauville score (DS) in therapy response assessment and to define the prognostic value of the metabolic response of end of induction (EOI) [18F]FDG PET (PET) in follicular lymphoma patients. METHODS: Adult patients with untreated grade 1-3a FL/ stage II-IV enrolled in the multicentre, prospective, phase III FOLL12 trial (NCT02063685) were randomized to receive standard immunochemotherapy followed by rituximab maintenance (standard arm) versus standard immunochemotherapy followed by response-adapted post-induction management (experimental arm). Baseline and EOI PET were mandatory for the study. All PET scans were centralized on the WIDEN® platform and classified according to DS in a blind independent central review. DS1-3 was considered negative (CMR), whereas DS4-5 was considered positive (not CMR). The primary endpoint was PFS. The main secondary endpoint was overall survival (OS). RESULTS: Overall, 807 follicular lymphoma patients-52% women, 89% stage III-IV disease, 40% with a high-risk FLIPI-2 score (3-5)-were enrolled in the study; 729 (90.4%) baseline and EOI PET were available for the analysis. EOI PET was positive (DS4-5) in 88/729 (12.1%) cases. Overall inter-reviewer agreement on PET pos/neg result was 0.92, while agreement on positive and negative cases was 0.77 and 0.94, respectively. The median follow-up was 69 months; 247 events were registered in the 5-yr follow-up, with a 5-yr PFS of 67% (95%CI: 63%-70%). The 5-yr PFS rate for PET neg (DS1-3) and PET pos (DS4-5) patients was 71% (95%CI: 67%-75%) and 36% (95%CI: 25%-46%), respectively, with HR 3.49 (95%CI: 2.57-4.72). Five-year PFS was worse as DS increased, with 74% (70%-78%), 58% (48%-67%; HR 1.71; p = 0.001)] and 36% (25%-46%; HR 3.88; p < 0.001) in DS1-2, DS3 and DS4-5, respectively. EOI PET maintained its prognostic value in both the standard and experimental arms. In the whole population, 5-yr OS was 94% (95%CI: 92%-96%), with 96% (95%CI: 94-97) and 82% (95%CI: 72%-89%) in EOI PET negative (DS1-3) and positive (DS4-5), respectively (HR 4.48; p < 0.001). When DS was associated with FLIPI-2, patients with DS3 or DS1-2 with high FLIPI-2 (3-5) experienced worse OS than patients with DS1-2 and low FLIPI-2 (1-2) (p = 0.003). CONCLUSION: This study shows that DS is a reliable prognostic tool to evaluate EOI PET in follicular lymphoma patients, with prognostic value maintained both in the standard and experimental arms, making metabolic imaging a robust tool to assess response in FL. Moreover, although preliminary, this study provides further information on DS3 patients, who are considered as CMR but show a less favourable PFS than DS1-2 patients.

Brentuximab Vedotin and Bendamustine Produce Long-Term Clinical Benefit in Patients With Relapsed or Refractory Classical Hodgkin Lymphoma: A Multicenter Real-Life Experience.

BACKGROUND: Patients with relapsed or refractory classical Hodgkin lymphoma (R/R cHL) have limited opportunities for curative therapy. High-dose therapy followed by autologous stem cell transplantation (HDT-ASCT) produces cure rates of 50% to 60%. Patients relapsing after, or ineligible for HDT-ASCT have limited therapeutic options and long-term remission is uncommon. Furthermore, few patients are candidate to allogeneic stem cell transplantation (AlSCT), a potentially curative approach. The combination of brentuximab vedotin and bendamustine (BVB) is a promising treatment for patients with R/R cHL, regardless of SCT eligibility. PATIENTS AND METHODS: We conducted a real-life study of BVB in 41 patients with R/R cHL after failure of ≥ 1 therapy including ASCT, AlSCT, or BV. RESULTS: Among 40 patients evaluable for efficacy, the overall response rate and complete response (CR) rate were 75% and 50%, respectively. No significant differences were observed between patients with primary refractory and relapsed disease, previously treated with ≤ 2 and ≥ 3 lines of therapy, or BV-exposed and BV-naïve. After a median follow-up of 38 months, the median progression free survival (PFS) for the entire population is 26 months; PFS is not reached, 10.5 months, and 4 months for patients achieving CR, partial response and no response, respectively (P < .0001). BVB was well tolerated and no grade 4 toxicity or new safety signals were observed. The most common treatment-emergent adverse events were infections. CONCLUSION: Our experience supports the efficacy and tolerability of the BVB combination in R/R cHL as a bridge to SCT, or as a definitive therapy for SCT-ineligible patients. Larger comparative studies testing BVB against standards of care are warranted in both settings.

Response-Adapted Postinduction Strategy in Patients With Advanced-Stage Follicular Lymphoma: The FOLL12 Study.

PURPOSE: We compared 2 years of rituximab maintenance (RM) with a response-adapted postinduction approach in patients with follicular lymphoma who responded to induction immunochemotherapy. METHODS: We randomly assigned treatment-naïve, advanced-stage, high-tumor burden follicular lymphoma patients to receive standard RM or a response-adapted postinduction approach on the basis of metabolic response and molecular assessment of minimal residual disease (MRD). The experimental arm used three types of postinduction therapies: for complete metabolic response (CMR) and MRD-negative patients, observation; for CMR and MRD-positive (end of induction or follow-up) patients, four doses of rituximab (one per week, maximum three courses) until MRD-negative; and for non-CMR patients, one dose of ibritumomab tiuxetan followed by standard RM. The study was designed as noninferiority trial with progression-free survival (PFS) as the primary end point. RESULTS: Overall, 807 patients were randomly assigned. After a median follow-up of 53 months (range, 1-92 months), patients in the standard arm had a significantly better PFS than those in the experimental arm (3-year PFS 86% v 72%; P < .001). The better PFS of the standard versus experimental arm was confirmed in all the study subgroups except non-CMR patients (n = 65; P = .274). The 3-year overall survival was 98% (95% CI, 96 to 99) and 97% (95% CI, 95 to 99) in the reference and experimental arms, respectively (P = .238). CONCLUSION: A metabolic and molecular response-adapted therapy as assessed in the FOLL12 study was associated with significantly inferior PFS compared with 2-year RM. The better efficacy of standard RM was confirmed in the subgroup analysis and particularly for patients achieving both CMR and MRD-negative.

A brief rituximab, bendamustine, mitoxantrone (R-BM) induction followed by rituximab consolidation in elderly patients with advanced follicular lymphoma: a phase II study by the Fondazione Italiana Linfomi (FIL).

Treatment for follicular lymphoma (FL) in the elderly is not well standardized. A phase II, multicentre, single arm trial was conducted in this setting with a brief chemoimmunotherapy regimen. Treatment consisted in four monthly courses of rituximab, bendamustine and mitoxantrone (R-BM) followed by 4 weekly rituximab as consolidation; rituximab maintenance was not applied because the drug was not licensed at the time of enrolment. The primary endpoint was the complete remission rate (CR). Seventy-six treatment-naive FL patients (aged 65-80 and a "FIT" score, according to the Comprehensive Geriatric Assessment) were enrolled. CR was documented in 59/76 patients (78%), partial remission in 12 (16%) and stable/progressive disease in five (6%) with an overall response rate in 71/76 (94%). Median follow-up was 44 months with 3-year progression-free-survival (PFS) and overall-survival of 67% and 92% respectively. Nine deaths occurred, three of progressive disease. The regimen was well tolerated and the most frequent severe toxicity was neutropenia (18% of the cycles). Bcl-2/IGH rearrangement was found in 40/75 (53%) of evaluated patients. R-BM was highly effective in clearing polymerase chain reaction-detectable disease: 29/31 (96%) evaluated patients converted to bcl-2/IGH negativity at the end of treatment. A brief R-BM regimen plus rituximab consolidation is effective and safe in "FIT" elderly, treatment-naïve, FL patients, inducing high CR and molecular remission rates with prolonged PFS.

The neutrophil to lymphocyte ratio (NLR) and the presence of large nodal mass are independent predictors of early response: A subanalysis of the prospective phase II PET-2-adapted HD0607 trial.

BACKGROUND: The neutrophil to lymphocyte ratio (NLR) and the lymphocyte to monocyte ratio (LMR) can reflect both the myeloid dysfunction and T-cell immune suppression and have prognostic significance. METHODS: In 771 newly diagnosed advanced-stage Hodgkin Lymphoma (HL) patients we evaluated the baseline values of NLR and LMR as predictors of clinical outcome. According to the multicenter prospective phase II GITIL-HD0607 trial, all patients received two ABVD courses and if PET-2 negative received four additional ABVD cycles while if PET-2-positive patients were randomized to either BEACOPP escalated (Be) plus BEACOPP baseline (Bb) (4 + 4 courses) or Be + Bb (4 + 4) and Rituximab. PET scans were centrally reviewed by an expert panel by Blinded Independent Central Review. RESULTS: Higher NLR and lower LMR were associated with a PET-2 positivity and failure to achieve long-term disease control, respectively. By univariate and multivariate analysis, large nodal mass (>7 cm), IPS ≥ 3, NLR > 6 were strong independent predictors of early PET-2 response after ABVD. Only NLR > 6 and IPS ≥ 3 were strong independent predictors of outcome at diagnosis; however, when PET-2 status was added, only PET-2-positive status and IPS ≥ 3 were independent predictors of PFS. Focusing on PET-2-negative patients, those with NLR > 6 had an inferior 3-year PFS compared to patients with NLR ≤ 6 (84% vs 89% months, P = .03). CONCLUSION: In advanced-stage HL patients treated with a PET-2-driven strategy, IPS ≥ 3 and NLR > 6 are independent predictors of outcome at diagnosis while the presence of large nodal mass, IPS ≥ 3, and NLR > 6 at diagnosis are independent predictors of early ABVD response.

Consolidation Radiotherapy Could Be Safely Omitted in Advanced Hodgkin Lymphoma With Large Nodal Mass in Complete Metabolic Response After ABVD: Final Analysis of the Randomized GITIL/FIL HD0607 Trial.

PURPOSE: To investigate the role of consolidation radiotherapy (cRT) in advanced-stage Hodgkin lymphoma (HL) presenting at baseline with a large nodal mass (LNM) in complete metabolic response after doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy. PATIENTS AND METHODS: Advanced-stage (IIB-IVB) HL patients, enrolled in the HD 0607 trial (Clinicaltrial.gov identifier NCT00795613), with both a negative PET after two (PET-2) and six (PET-6) ABVD cycles, who presented at baseline with an LNM, defined as a nodal mass with the largest diameter ≥ 5 cm, were prospectively randomly assigned to receive cRT over the LNM or no further treatment (NFT). RESULTS: Among 296 randomly assigned patients, the largest diameter of LNM at baseline was 5-7 cm in 101 (34%; subgroup A) and 8-10 cm in 96 (32%; subgroup B), whereas classic bulky (diameter > 10 cm) was detected in 99 (33%; subgroup C). Two hundred eighty patients (88%) showed a postchemotherapy RM. The median dose of cRT was 30.6 Gy (range, 24-36 Gy). After a median follow-up of 5.9 years (range, 0.5-10 years), the 6-year progression-free survival rate of patients who underwent cRT or NFT was, respectively, 91% (95% CI, 84% to 99%) and 95% (95% CI, 89% to 100%; P = .62) in subgroup A; 98% (95% CI, 93% to 100%) and 90% (95% CI, 80% to 100%; P = .24) in subgroup B; 89% (95% CI, 81% to 98%) and 86% (95% CI, 77% to 96%; P = .53) in subgroup C (classic bulky). CONCLUSION: cRT could be safely omitted in patients with HL presenting with an LNM and a negative PET-2 and PET-6 scan, irrespective from the LNM size detected at baseline.

Nonpeghylated liposomal doxorubicin combination regimen (R-COMP) for the treatment of lymphoma patients with advanced age or cardiac comorbidity.

Doxorubicin is the most effective single agent in the treatment of non-Hodgkin's lymphoma (NHL). Its use is limited because of the cardiac toxicity primarily in elderly patients (pts) and in pts with history of cardiac disease. Liposomal doxorubicin has been proven to reduce cardiotoxicity. The aim of this retrospective study was the use of nonpeghylated liposomal doxorubicin (NPLD) in term of efficacy, response rate and incidence of cardiac events. We retrospectively collected the experience of 33 Hematological Italian Centers in using NPLD. Nine hundred and forty-six consecutive pts treated with R-COMP (doxorubicin was substituted with NPLD, Myocet) were collected. Median age was 74 years, the reasons for use of NPLD were: age (466 pts), cardiac disease (298 pts), uncontrolled hypertension (126 pts), other reasons (56 pts). According to clinicians' evaluation, 49.9% of pts would not have used standard doxorubicin for different situations (age, cardiomyopathy, previous use of doxorubicin, and uncontrolled hypertension). Overall 687 pts (72.6%) obtained a complete remission (CR). About 5% (n = 51) of subjects developed major cardiotoxic events including heart failure (N = 31), ischemic heart disease (N = 16), acute heart attack (N = 3), and acute pulmonary oedema (N = 1). After a median follow-up of 32 months, 651 pts were alive and the overall survival (OS) was 72%. After a median observation period of 23 months disease free survival (DFS) was 58%. Either in univariate or in multivariate analysis OS and DFS were not significantly affected by age or cardiac disease. Our findings strongly support that including R-COMP is effective and safe when the population is at high risk of cardiac events and negatively selected. Moreover, the use of this NPLD permitted that about half of our population had the opportunity to receive the best available treatment.

Early Chemotherapy Intensification With Escalated BEACOPP in Patients With Advanced-Stage Hodgkin Lymphoma With a Positive Interim Positron Emission Tomography/Computed Tomography Scan After Two ABVD Cycles: Long-Term Results of the GITIL/FIL HD 0607 Trial.

Purpose To investigate the progression-free survival (PFS) of patients with advanced Hodgkin lymphoma (HL) after a risk-adapted treatment strategy that was based on a positive positron emission tomography scan performed after two doxorubicin, vinblastine, vincristine, and dacarbazine (ABVD) cycles (PET2). Patients and Methods Patients with advanced-stage (IIB to IVB) HL were consecutively enrolled. After two ABVD cycles, PET2 was performed and centrally reviewed according to the Deauville five-point scale. Patients with a positive PET2 were randomly assigned to four cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) followed by four cycles of standard BEACOPP with or without rituximab. Patients with a negative PET2 continued ABVD, and those with a large nodal mass at diagnosis (≥ 5 cm) in complete remission with a negative PET at the end of chemotherapy were randomly assigned to radiotherapy or no further treatment. The primary end point was 3-year PFS. Results Of 782 enrolled patients, 150 (19%) had a positive and 630 (81%) a negative PET2. The 3-year PFS of all patients was 82%. The 3-year PFS of those with a positive and negative PET2 was 60% and 87%, respectively ( P < .001). The 3-year PFS of patients with a positive PET2 assigned to BEACOPP with or without rituximab was 63% versus 57% ( P = .53). In 296 patients with both interim and post-ABVD-negative PET who had a large nodal mass at diagnosis, radiotherapy was randomly added after chemotherapy without a significant PFS improvement (97% v 93%, respectively; P = .29). The 3-year overall survival of all 782 patients was 97% (99% and 89% for PET2 negative and positive, respectively). Conclusion The PET-driven switch from ABVD to escalated BEACOPP is feasible and effective in high-risk patients with advanced-stage HL.

Prognostic Value of Bone Marrow Tracer Uptake Pattern in Baseline PET Scans in Hodgkin Lymphoma: Results from an International Collaborative Study.

PET/CT-ascertained bone marrow involvement (BMI) constitutes the single most important reason for upstaging by PET/CT in Hodgkin lymphoma (HL). However, BMI assessment in PET/CT can be challenging. This study analyzed the clinicopathologic correlations and prognostic meaning of different patterns of bone marrow (BM) 18F-FDG uptake in HL. Methods: One hundred eighty newly diagnosed early unfavorable and advanced-stage HL patients, all scanned at baseline and after 2 adriamycin-bleomycin-vinblastine-dacarbazine (ABVD) courses with 18F-FDG PET, enrolled in 2 international studies aimed at assessing the role of interim PET scanning in HL, were retrospectively included. Patients were treated with ABVD × 4-6 cycles and involved-field radiation when needed, and no treatment adaptation on interim PET scanning was allowed. Two masked reviewers independently reported the scans. Results: Thirty-eight patients (21.1%) had focal lesions (fPET+), 10 of them with a single (unifocal) and 28 with multiple (multifocal) BM lesions. Fifty-three patients (29.4%) had pure strong (>liver) diffuse uptake (dPET+) and 89 (48.4%) showed no or faint (≤liver) BM uptake (nPET+). BM biopsy was positive in 6 of 38 patients (15.7%) for fPET+, in 1 of 53 (1.9%) for dPET+, and in 5 of 89 (5.6%) for nPET+ dPET+ was correlated with younger age, higher frequency of bulky disease, lower hemoglobin levels, higher leukocyte counts, and similar diffuse uptake in the spleen. Patients with pure dPET+ had a 3-y progression-free survival identical to patients without any 18F-FDG uptake (82.9% and 82.2%, respectively, P = 0.918). However, patients with fPET+ (either unifocal or multifocal) had a 3-y progression-free survival significantly inferior to patients with dPET+ and nPET+ (66.7% and 82.5%, respectively, P = 0.03). The κ values for interobserver agreement were 0.84 for focal uptake and 0.78 for diffuse uptake. Conclusion: We confirmed that 18F-FDG PET scanning is a reliable tool for BMI assessment in HL, and BM biopsy is no longer needed for routine staging. Moreover, the interobserver agreement for BMI in this study proved excellent and only focal 18F-FDG BM uptake should be considered as a harbinger of HL.

Implemented myeloma management with whole-body low-dose CT scan: a real life experience.

A total of 318 consecutive myeloma patients underwent whole-body low-dose CT scan (WBLDCT) at baseline and during follow-up as a radiological assessment of lytic lesions in place of skeletal X-ray survey. After WBLDCT baseline assessment, 60% had bone involvement. The presence of lytic lesions represented the only met CRAB (hyperCalcaemia, Renal insufficiency, Anaemia, Bone lesions) criteria in 29% of patients. Patients presenting with extramedullary masses were 10%. Radiological progression was documented in 9% of the population with available follow-up. Additional pathological incidental findings were detected in 28 patients (14.5%), most located in the chest region (68%). In conclusion, our real-life data shows that WBLDCT scan represents a reliable imaging tool for decision-making process for multiple myeloma management in different disease phases, providing significant additional information on the presence of soft tissues plasmacytomas detection as well as the presence of pathological incidental findings.

Peripheral blood lymphocyte/monocyte ratio predicts outcome in follicular lymphoma and in diffuse large B-cell lymphoma patients in the rituximab era.

BACKGROUND: Diffuse large B-cell lymphoma is an aggressive lymphoma and a large number of studies have therefore focused on the search for prognostic factors. The same interest concerns FL, for which identification of patients candidates for watch and wait (W&W) strategy is still an option. Studies about the number and type of lymphocytes and monocytes detectable in patients with Hodgkin and non-Hodgkin lymphomas indicate they might affect the pathogenesis and prognosis of these diseases. LMR is recently under investigation as a new prognostic parameter in DLBCL; the role of this ratio in FL in the rituximab era is unknown. PATIENTS AND METHODS: We retrospectively analyzed 137 DLBCL and 132 FL patients referred to our institution; among FL pts, a W&W approach was performed at diagnosis for 42 patients. The remaining patients were treated with rituximab-containing therapy. We analyzed different LMR cutoff values at diagnosis and we wanted to investigate the prognostic effect among DLBCL and FL. RESULTS: We found that the most discriminative LMR was 2.4 for DLBCL and 2 for FL. Among DLBCL patients, an LMR value < 2.4 was associated with a worse 2-year progression-free survival (PFS), and we observed no difference in overall survival and complete response rate. Considering FL patients, LMR > 2 was associated with a longer time to treatment start compared with the LMR < 2 group (P = .0096). Among the 92 patients treated with rituximab chemotherapy, 2-year PFS was superior in the LMR > 2 group. CONCLUSION: LMR at diagnosis is a simple tool to better define long-term outcome of DLBCL and FL patients. The use of this tool might better define selection in FL of ideal candidates for W&W strategy.

The use of anthracycline at first-line compared to alkylating agents or nucleoside analogs improves the outcome of salvage treatments after relapse in follicular lymphoma The REFOLL study by the Fondazione Italiana Linfomi.

Follicular lymphoma (FL) patients experience multiple remissions and relapses and commonly receive multiple treatment lines. A crucial question is whether anthracyclines should be used at first-line or whether they would be better "reserved" for relapse and whether FL outcome can be optimized by definite sequences of treatments. Randomized trials can be hardly designed to address this question. In this retrospective multi-institutional study, time-to-next-treatment after first relapse was analyzed in 510 patients who had received either alkylating agents- or anthracycline- or nucleoside analogs-based chemotherapy with/without rituximab at first-line and different second-line therapies. After a median of 42 months, median time-to-next-treatment after relapse was 41 months (CI95%:34-47 months). After adjustment for covariates, first-line anthracycline-based chemotherapy with/without rituximab was associated with better time-to-next-treatment after any salvage than alkylating agents-based chemotherapy with/without rituximab or nucleoside analogs-based chemotherapy with/without rituximab (HR:0.74, P = 0.027). The addition of rituximab to first-line chemotherapy had no significant impact (HR:1.22, P = 0.140). Autologs stem cell transplantation performed better than any other salvage treatment (HR:0.53, P < 0.001). First-line anthracycline-based chemotherapy significantly improved time-to-next-treatment even in patients receiving salvage autologs stem cell transplantation (P = 0.041). This study supports the concept that in FL previous treatments significantly impact on the outcome of subsequent therapies. The outcome of second-line treatments, either with salvage chemoimmunotherapy or with autologs stem cell transplantation, was better when an anthracycline-containing regimen was used at first-line.

The predictive role of interim positron emission tomography for Hodgkin lymphoma treatment outcome is confirmed using the interpretation criteria of the Deauville five-point scale.

A retrospective, international, multicenter study was undertaken to assess: (i) the prognostic role of 'interim' positron emission tomography performed during treatment with doxorubicin, bleomycin, vinblastine and dacarbazine in patients with Hodgkin lymphoma; and (ii) the reproducibility of the Deauville five-point scale for the interpretation of interim positron emission tomography scan. Two hundred and sixty patients with newly diagnosed Hodgkin lymphoma were enrolled. Fifty-three patients with early unfavorable and 207 with advanced-stage disease were treated with doxorubicin, bleomycin, vinblastine and dacarbazine ± involved-field or consolidation radiotherapy. Positron emission tomography scan was performed at baseline and after two cycles of chemotherapy. Treatment was not changed according to the results of the interim scan. An international panel of six expert reviewers independently reported the scans using the Deauville five-point scale, blinded to treatment outcome. Forty-five scans were scored as positive (17.3%) and 215 (82.7%) as negative. After a median follow up of 37.0 (2-110) months, 252 patients are alive and eight have died. The 3-year progression-free survival rate was 83% for the whole study population, 28% for patients with interim positive scans and 95% for patients with interim negative scans (P<0.0001). The sensitivity, specificity, and negative and positive predictive values of interim positron emission tomography scans for predicting treatment outcome were 0.73, 0.94, 0.94 and 0.73, respectively. Binary concordance amongst reviewers was good (Cohen's kappa 0.69-0.84). In conclusion, the prognostic role and validity of the Deauville five-point scale for interpretation of interim positron emission tomography scans have been confirmed by the present study.

Chemoresistance as a function of the pretherapy tumor burden and the chemotherapy regimen administered: differences observed with 2 current chemotherapy regimens for advanced Hodgkin lymphoma.

BACKGROUND: The mature results from trials comparing ABVD (Adriamycin [doxorubicin], bleomycin, vinblastine, dacarbazine) and BEACOPP (bleomycin, etoposide, Adriamycin [doxorubicin], cyclophosphamide, Oncovin [vincristine], procarbazine, prednisone) chemotherapies in advanced Hodgkin lymphoma will be available in some years. An early comparison of their curative potential can however be obtained from an assessment of initial tumor burden and chemoresistance. PATIENTS AND METHODS: Less than a complete remission after treatment and relapse occurring within 12 months thereafter were assumed to be clinical expressions of chemoresistance. The tumor burden was calculated from the measurements of all the lesions documented by staging computed tomography (CT) and was normalized to body surface area to give the relative tumor burden (rTB). Using logistic regression analysis, the relationship between initial rTB, chemoresistance, and chemotherapy regimen administered was retrospectively studied in 222 patients selected from those enrolled in 2 similar randomized trials. RESULTS: The median rTB volumes were 157.9 cm(3)/m(2) in the 115 patients treated with ABVD vs. 154.6 cm(3)/m(2) in the 107 patients treated with BEACOPP, and the distribution of the volumes was identical in the 2 groups. The rTB was confirmed as the best predictor of early treatment failures (22 less than complete responses plus 21 early relapses). For the same rTB, the risk of chemoresistance to BEACOPP was about half that of the chemoresistance to ABVD or, for a given risk of chemoresistance, BEACOPP cured patients with an rTB 89.1 cm(3)/m(2) greater than that cured by ABVD (ie, more than 50% of the median tumor load of patients with advanced-stage disease). CONCLUSION: This account of rTB allows an early comparative evaluation of the curative ability of different chemotherapy regimens.

Effects of music therapy on psychological symptoms and heart rate variability in patients with dementia. A pilot study.

We assessed the effects of music therapy (MT) on behavioral and psychological symptoms (BPSD) in dementia associated with changes in physiological parameters, as heart rate (HR) and heart rate variability (HRV). Twenty subjects were randomly assigned to MT treatment or standard care; all patients underwent neuropsychological assessment and ECG Holter recordings before and after the 15-week treatment. The treatment included 30 MT sessions. Depression significantly decreased (p=0.021) in the MT group. PNN50 improved in 50% patients of the MT group, but in none of the control group (p=0.013). MT may improve symptoms of depression and increase HRV in demented patients.