FDG-PET/CT predicts outcome in patients with aggressive non-Hodgkin’s lymphoma and Hodgkin’s disease

Early therapy response assessment with metabolic imaging is potentially useful to determine prognosis in aggressive lymphoma and, thus, can guide first-line therapy. Forty-eight patients with aggressive lymphoma [24 Hodgkin’s disease (HD); 24 non-Hodgkin’s lymphoma (NHL)] underwent fluoro-deoxyglucose positron emission tomography (FDG-PET) before chemotherapy (PET1) and at mid-treatment (PET2). Therapeutic response was evaluated using conventional methods at mid-treatment. PET2 results were related to event-free survival (EFS) and overall survival (OS) using Kaplan–Meier analyses. PET1 was positive in all patients. PET2 was negative in 38 patients (18 NHL-20 HD) and positive in 10 (6 NHL-4 HD). Of the PET-negative patients, 61 and 65% achieved complete remission, and only 50 and 25% of PET-positive patients, respectively, for NHL and HD, achieved complete remission. Significant associations were found between PET2 and EFS (p=0.0006) and OS (p=0.04) for NHL, and EFS (p<0.0001) for HD (but not for OS, because no HD patient died). FDG-PET at mid-treatment can predict the outcome of patients with aggressive lymphoma and should be a useful tool to modify an ineffective therapy.     

Role of bone marrow biopsy in staging of patients with classical Hodgkin’s lymphoma undergoing positron emission tomography/computed tomography

Several studies suggested that staging bone marrow biopsy (BMB) could be omitted in patients with classical Hodgkin’s lymphoma (cHL) when a positron emission tomography/computed tomography (PET/CT) is performed at baseline.To address the concordance between BMB and PET/CT in the detection of bone marrow involvement (BMI) and the BMB role in determining the Ann Arbor stage, we retrospectively collected data on 1244 consecutive patients with cHL diagnosed from January 2007 to December 2013. One thousand eighty-five patients who had undergone both BMB and PET/CT were analyzed, comparing the Ann Arbor stage assessed with PET/CT only to that resulting from PET/CT combined with BMB.One hundred sixty-nine patients (16%) showed at least one focal skeletal lesion (FSL) at PET/CT evaluation. Only 55 patients had a positive BMB (5.1%); 34 of them presented at least one FSL at PET/CT. To the contrary, 895 out of 1030 patients with a negative BMB did not show any FSL (86.9%). Positive and negative predictive values of PET/CT for BMI were 20 and 98%, respectively; sensitivity and specificity were 62 and 87%, respectively. Fifty-four out of 55 patients with a positive BMB could have been evaluated as an advanced stage just after PET/CT; only one patient (0.1%) would have been differently treated without BMB.Our data showed a very high negative predictive value of PET/CT for BMI and a negligible influence of BMB on treatment planning, strengthening the recent indications that BMB could be safely omitted in cHL patients staged with PET/CT.     

Hodgkin’s lymphoma following treatment with etanercept in ankylosing spondylitis

It has been well known that anti-TNF drugs might increase lymphoma risk in rheumatoid arthritis (RA), where the rate of lymphoma has already been increased. However, unlike RA, an increased rate of lymphoma has not been reported in ankylosing spondylitis (AS). Hereby, we present a case with AS developing Hodgkin’s lymphoma (HL) following 6 months of etanercept treatment. Pathological analysis revealed mixed cellular type of HL. Although we report a single case, it should be kept in mind that anti-TNF drugs might cause lymphoma development not only in RA, but also in AS.     

Initial Staging of Hodgkin’s Disease: Role of Contrast-Enhanced 18F FDG PET/CT

The objective of this study was to compare the diagnostic accuracy of positron emission tomography/low-dose computed tomography (PET/ldCT) versus the same technique implemented by contrast-enhanced computed tomography (ceCT) in staging Hodgkin’s disease (HD).Forty patients (18 men and 22 women, mean age 30 ± 9.6) with biopsy-proven HD underwent a PET/ldCT study for initial staging including an unenhanced low-dose computed tomography for attenuation correction with positron emission tomography acquisition and a ceCT, performed at the end of the PET/ldCT scan, in the same exam session. A detailed datasheet was generated for illness locations for separate imaging modality comparison and then merged in order to compare the separate imaging method results (PET/ldCT and ceCT) versus merged results positron emission tomography/contrast-enhanced computed tomography (PET/ceCT). The nodal and extranodal lesions detected by each technique were then compared with follow-up data that served as the reference standard.No significant differences were found at staging between PET/ldCT and PET/ceCT in our series. One hundred and eighty four stations of nodal involvement have been found with no differences in both modalities. Extranodal involvement was identified in 26 sites by PET/ldCT and in 28 by PET/ceCT. We did not find significant differences concerning the stage (Ann Arbor).Our study shows a good concordance and conjunction between PET/ldCT and ceCT in both nodal and extranodal sites in the initial staging of HD, suggesting that PET/ldCT could suffice in most of these patients.     

Clinico-pathologic profile of Hodgkin’s lymphoma in a rural medical college

Purpose of study

A prospective study was done at North Bengal Medical College and Hospital (NBMCH), Darjeeling, West Bengal, which caters predominantly to the rural and hilly population. All patients diagnosed as Hodgkin’s lymphoma (HL) were analyzed for clinical presentation, histological classified and staging.

Results

Total of 48 cases reported for HL were studied (n=48). A lower median age of onset (28.1year) and higher male to female ratio (3.8:1) as compared to western countries were observed. We found neck swelling was the commonest presenting symptom (58.28%) and peripheral lymphadenopathy was the commonest sign (83.33%). “B symptoms” was noted in 79.17% cases. Cervical lymph nodes were commonly involved (79.17%), followed by inguinal (45.83%) and axillary (29.17%). Thoracic lymph nodes and abdominal lymph nodes were enlarged in 29.17% of the cases and 25% of the cases respectively. Eosinophilia was noted in 29.17% of cases. Marrow involvement by neoplastic process was observed in 8.33% of cases and reactive changes in the marrow were observed in 12.5% of cases. We found mixed cellularity subtypes was the commonest (45.83%) followed by nodular sclerosis subtypes (33.33%). At presentation 54.17% of cases were of advanced stage of disease (stage III and IV).

Conclusion

We noticed a distinct geographical pattern of HL in respect of age, sex, presentation, histological typing and staging of the disease, which is comparable to some other Indian studies but is noticeably different from patterns noted in Western countries.

     

Unsuspected FDG–PET findings in the follow-up of patients with lymphoma

18F-Fluorodeoxyglucose–positron emission tomography (FDG–PET) plays an increasing role in the management of patients with lymphoma, for which it is successfully used for staging and treatment monitoring. We report seven patients with a history of lymphoma who presented a positive FDG–PET suggestive of lymphoma relapse and for which FDG–PET oriented biopsies revealed alternative diagnoses. Early in lymphoma follow-up, persistence of focal increased FDG activity corresponded to inflammatory or infectious lesions in two patients: one aspergillosis and one sarcoidosis. Later in the follow-up, five cases of secondary malignancies were identified (three lung cancers, one epidermoid carcinoma, and one villous tumor) in this particularly exposed population. The routine use of FDG PET to evaluate lymphoma significantly increases the probability of detecting unexpected diseases. These cases illustrate the potential pitfalls in PET follow-up. Because FDG is not lymphoma-specific, a relapse suspected only on FDG–PET imaging requires biopsy, as alternative diagnoses—infectious or malignant—are possible. Our data draws clinician’s attention to potential false–positive FDG–PET findings, which may lead to therapeutic mistakes. Our data also suggests that FDG–PET might be a new imaging modality for long-term monitoring of late effects, especially second cancer occurrence.     

Sperm quality before treatment in patients with early stage Hodgkin’s lymphoma enrolled in EORTC-GELA Lymphoma Group trials

Background

Although widely recommended, cryopreservation of sperm is sometimes not performed for patients with Hodgkin’s lymphoma because of presumed poor sperm quality related to the disease. We investigated sperm quality and factors determining it in untreated patients with early stage Hodgkin’s lymphoma.

Design and Methods

Of 2362 males who participated in EORTC H6–H9 trials, 474 (20%) had data available. Sperm quality was defined according to World Health Organization guidelines. Determining factors were studied by logistic regression analysis.

Results

The median sperm concentration was 40×10⁶/mL (range, 0–345×10⁶/mL) and the median motility 50% (range, 0–90%). Sperm quality was good (concentration ≥20×10⁶/mL and motility ≥50%), intermediate (concentration ≥5×10⁶/mL) and poor (concentration <5×10⁶/mL but >0) in 41%, 49% and 7% of patients, respectively. Three percent of the patients were azoospermic. No relation was found between sperm quality and age or clinical stage of the Hodgkin’s lymphoma, but B-symptoms and elevated erythrocyte sedimentation rate predicted poor sperm quality. The odds ratios for the association of poor sperm quality with the variables examined were: presence of B-symptoms, 2.77 (95% CI, 1.50–5.12; p=0.001); erythrocyte sedimentation rate of 50 mm/h or greater, 2.35 (95% CI, 1.24–4.43; p=0.009); fever, 3.22 (95% CI, 1.41–7.33; p=0.005), and night sweats, 3.78 (95% CI, 1.97–7.26; p<0.001). There was no relation between sperm quality and pre-treatment follicle stimulating hormone level.

Conclusions

In this large study of males with Hodgkin’s lymphoma, 90% had good or intermediate sperm quality. Three percent were azoospermic. There was an association between sperm quality and the presence or absence of B-symptoms, in particular fever and night sweats. With modern fertilization techniques, in most patients with early-stage Hodgkin’s lymphoma sperm quality before treatment is good enough for future fatherhood.     

Multicenter phase II study of plitidepsin in patients with relapsed/refractory non-Hodgkin’s lymphoma

This phase II clinical trial evaluated the efficacy, safety and pharmacokinetics of plitidepsin 3.2 mg/m² administered as a 1-hour intravenous infusion weekly on days 1, 8 and 15 every 4 weeks in 67 adult patients with relapsed/refractory aggressive non-Hodgkin’s lymphoma. Patients were divided into two cohorts: those with non-cutaneous peripheral T-cell lymphoma (n=34) and those with other lymphomas (n=33). Efficacy was evaluated using the International Working Group criteria (1999). Of the 29 evaluable patients with non-cutaneous peripheral T-cell lymphoma, six had a response (overall response rate 20.7%; 95% confidence interval, 8.0%–39.7%), including two complete responses and four partial responses. No responses occurred in the 30 evaluable patients with other lymphomas (including 27 B-cell lymphomas). The most common plitidepsin-related adverse events were nausea, fatigue and myalgia (grade 3 in <10% of cases). Severe laboratory abnormalities (lymphopenia, anemia, thrombocytopenia, and increased levels of transaminase and creatine phosphokinase) were transient and easily managed by plitidepsin dose adjustments. The pharmacokinetic profile did not differ from that previously reported in patients with solid tumors. In conclusion, plitidepsin monotherapy has clinical activity in relapsed/refractory T-cell lymphomas. Combinations of plitidepsin with other chemotherapeutic drugs deserve further evaluation in patients with non-cutaneous peripheral T-cell lymphoma. (clinicaltrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT00884286","term_id":"NCT00884286"}}NCT00884286)     

Positron emission tomography in the staging of patients with Hodgkin’s lymphoma. A prospective multicentric study by the Intergruppo Italiano Linfomi

In this prospective multicentric study, we investigated the contribution of positron emission tomography (PET) scanning to the staging of Hodgkin’s lymphoma (HL) by computed tomography (CT) and attempted to determine whether it has any impact on therapeutic approach. One hundred eighty six consecutive patients with HL from six Italian centers were enrolled in this study. They were staged with conventional methods; 2-[fluorine-18]fluoro-2-deoxy-d-glucose PET scanning were prospectively compared to CT. CT and FDG-PET stages were concordant in 156 patients (84%) and discordant in 30 patients (16%). PET stage in comparison to CT stage was higher in 27 patients (14%) and lower in 3 patients (1%). The programmed treatment strategy was modified in 11 out of 30 patients (37%) after the definition of final stage. If we considered the 123 CT staged patients with localized stage, ten patients (8%) with a change of stage from localized to advanced after PET evaluation were treated with different strategy. FDG-PET was shown to be a relevant, non-invasive method that supplements conventional procedures and should therefore be used routinely to stage HL, particularly in early stage patients, where a change in stage may modify disease management.     

High titres of IgM-antiphospholipid antibodies are unrelated to pathogenicity in patients with non-Hodgkin’s lymphoma

Heterogeneity in the mechanisms of coagulation may contribute to an increased thrombotic risk for patients with malignancies. The coincidence of malignancies and antiphospholipid antibodies (aPL) have been described in several important epidemiological studies. The pathological significance of aPL in patients with malignancies is, however, still unclear. In this study, we investigated the clinical manifestations of four patients with elevated IgM-aPL titres lying outside the region signifying 95% of normal cases and with a history of non-Hodgkin's lymphoma. The patients had elevated IgG- and IgM-anticardiolipin antibodies (aCL) and also tested positive for lupus anticoagulants. Other aPL were measured, and we found high positive results for all tested antibodies in three patients. The production of aPL, however, occurred in the absence of thrombotic complications. No thromboembolic manifestations occurred during the follow-up period either. It could also be demonstrated that the degree to which the aCL titre was elevated resembles the elevation of the non-classical antiphospholipid antibodies, but not that of beta2-GP-1 or anti-annexin antibodies. Therefore, it can be postulated that these extremely high levels of IgM-aCL antibodies do not enhance the risk of thrombosis and may be completely different from aCL antibodies in an antiphospholipid syndrome patient population without malignancies. In particular, haematological and lymphoproliferative malignancies may indeed be associated with the generation of aPL, but do not necessarily enhance the thrombophilic risk in these patients.     

Family history of lymphoma and risk for solid tumors in patients with Sjogren’s syndrome

It has been recognized that primary Sjogren’s syndrome predisposes to the development of lymphoproliferative disorders. However, it is so far uncertain whether these patients are at an increased risk for solid tumors. Herein we report two cases of primary Sjogren’s syndrome complicated by breast and lung cancer and who have a strong family history for lymphoproliferative diseases.     

Prognostic impact of bleomycin-induced pneumonitis on the outcome of Hodgkin’s lymphoma

Bleomycin-induced pneumonitis (BIP) has been well described in Hodgkin’s lymphoma (HL) patients. The impact of BIP on patients uniformly treated with adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) is not clear; previous studies have included patients treated with both ABVD and hybrid regimens. We reviewed our experience with BIP in HL to better understand the impact of BIP on overall survival. One hundred and eighty four consecutive patients who were treated with ABVD for newly diagnosed HL were eligible for retrospective review. BIP was defined by the presence of pulmonary symptoms, bilateral interstitial infiltrates on chest X-ray, computed tomography or presence of lung fibrosis on transbronchial lung biopsy, and the absence of infection. Patients were required to meet all three criteria to be included in the BIP group. BIP was observed in 28 patients (15%). A low albumin level and the use of colony granulocyte stimulating factor were associated with a higher risk of developing BIP. Age, smoking history, and underlying lung function were not predictive of BIP. Importantly, patients with BIP had similar rates of 5-year overall survival compared to unaffected patients. There were no deaths from BIP. Omission of bleomycin from subsequent treatment did not adversely affect the outcomes.