Ilse Christiansen

Routine Bone Marrow Biopsy Has Little or No Therapeutic Consequence for Positron Emission Tomography/Computed Tomography–Staged Treatment-Naive Patients With Hodgkin Lymphoma

PURPOSE To investigate whether bone marrow biopsy (BMB) adds useful information to [(18)F]fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) staging in patients with Hodgkin lymphoma (HL). PATIENTS AND METHODS Newly diagnosed patients with HL undergoing a pretherapeutic staging that encompasses both PET/CT and BMB were included in this retrospective study. The pattern of skeletal FDG uptake was categorized as uni-, bi-, or multifocal (≥ three lesions). Clinical stage, risk assessment, and treatment plan were determined with and without the contribution of BMB results according to the Ann Arbor classification and the guidelines from the German Hodgkin Study Group. RESULTS A total of 454 patients with HL were included of whom 82 (18%) had focal skeletal PET/CT lesions and 27 (6%) had positive BMB. No patients with positive BMB were assessed as having stage I to II disease by PET/CT staging. BMB upstaged five patients, assessed as being stage III before BMB; none of the 454 patients would have been allocated to another treatment on the basis of BMB results. Focal skeletal PET/CT lesions identified positive and negative BMBs with a sensitivity and specificity of 85% and 86%, respectively. The positive and negative predictive values of focal skeletal PET/CT lesions for BMB results were 28% and 99%, respectively. CONCLUSION A consistent finding of this study was the absence of positive BMBs in PET/CT-assessed stage I to II disease. The omission of staging BMB would not have changed the risk assessment or treatment strategy in this cohort of 454 newly diagnosed patients with HL.

Oral cladribine as primary therapy for patients with B-cell chronic lymphocytic leukemia.

PURPOSE Purine analogs have wide potential indications in the treatment of hematologic malignancies, but intravenous administration has been required. We previously established that the oral bioavailability of cladribine is 50%. Our aim was to evaluate the efficacy and toxicity of oral cladribine to previously untreated patients with chronic lymphocytic leukemia (CLL). PATIENTS AND METHODS Sixty-three patients with symptomatic but previously untreated CLL received cladribine solution 10 mg/m2/d orally for 5 consecutive days in monthly courses. RESULTS Complete remission (CR) was achieved in 24 patients (38%), and 23 patients (37%) had a partial response (PR). Most patients, including those in whom there was no remission (NR) achieved normal blood lymphocyte counts. Failure to meet response criteria was mostly due to thrombocytopenia. The median response duration was not reached at 2 years. The median survival time among 13 deceased patients was 322 days, whereas the median observation time of surviving patients is 760 days. The overall survival rate at 2 years is 82%. Response rate was associated with clinical stage. Grade III to IV infectious toxicity occurred in one third of patients. CONCLUSION Orally administered cladribine is an effective and feasible therapy for CLL, and produces durable remissions in three quarters of the patients. However, significant toxicity may occur and further studies are required to assess long-term effects and quality-of-life aspects.

Impact of age on survival after intensive therapy for multiple myeloma: a population-based study by the Nordic Myeloma Study Group.

The value of intensive therapy, including autologous stem cell transplantation, in newly diagnosed myeloma patients >60 years is not clear. We evaluated the impact of age (<60 years vs. 60–64 years) on survival in a prospective, population‐based setting and compared survival with conventionally treated historic controls. The prospective population comprised 452 patients registered between 1998 and 2000. Of these, 414 received intensive therapy. The historic population, derived from our most recent population‐based study on conventional therapy, comprised 281 patients. Of these, 243 fulfilled our eligibility criteria for intensive therapy. For patients undergoing intensive therapy it was found that two factors, beta‐2‐microglobulin and age <60 years vs. 60–64 years, had independent prognostic impact on survival. However, compared with the historic controls a survival advantage was found both for patients <60 (median 66 months vs. 43 months, P < 0·001) and 60–64 years (median 50 months vs. 27 months; P = 0·001). We conclude that in a population‐based setting higher age adversely influences outcome after intensive therapy. Our results indicate that intensive therapy prolongs survival also at age 60–64 years but with less superiority than in younger patients.

Positron emission tomography/computed tomography surveillance in patients with Hodgkin lymphoma in first remission has a low positive predictive value and high costs

Background The value of performing post-therapy routine surveillance imaging in patients with Hodgkin lymphoma is controversial. This study evaluates the utility of positron emission tomography/computed tomography using 2-[18F]fluoro-2-deoxyglucose for this purpose and in situations with suspected lymphoma relapse. Design and Methods We conducted a multicenter retrospective study. Patients with newly diagnosed Hodgkin lymphoma achieving at least a partial remission on first-line therapy were eligible if they received positron emission tomography/computed tomography surveillance during follow-up. Two types of imaging surveillance were analyzed: “routine” when patients showed no signs of relapse at referral to positron emission tomography/computed tomography, and “clinically indicated” when recurrence was suspected. Results A total of 211 routine and 88 clinically indicated positron emission tomography/computed tomography studies were performed in 161 patients. In ten of 22 patients with recurrence of Hodgkin lymphoma, routine imaging surveillance was the primary tool for the diagnosis of the relapse. Extranodal disease, interim positron emission tomography-positive lesions and positron emission tomography activity at response evaluation were all associated with a positron emission tomography/computed tomography-diagnosed preclinical relapse. The true positive rates of routine and clinically indicated imaging were 5% and 13%, respectively (P=0.02). The overall positive predictive value and negative predictive value of positron emission tomography/computed tomography were 28% and 100%, respectively. The estimated cost per routine imaging diagnosed relapse was US

Efficacy of routine surveillance with positron emission tomography/computed tomography in aggressive non-Hodgkin lymphoma in complete remission: status in a single center

50,778. Conclusions Negative positron emission tomography/computed tomography reliably rules out a relapse. The high false positive rate is, however, an important limitation and a confirmatory biopsy is mandatory for the diagnosis of a relapse. With no proven survival benefit for patients with a pre-clinically diagnosed relapse, the high costs and low positive predictive value make positron emission tomography/computed tomography unsuitable for routine surveillance of patients with Hodgkin lymphoma.

Elevated serum levels of soluble ICAM‐1 in non‐Hodgkin’s lymphomas correlate with tumour burden, disease activity and other prognostic markers

Post-therapy surveillance imaging in patients with lymphoma remains controversial. We report our experience with positron emission tomography/computed tomography (PET/CT) surveillance in patients with aggressive non-Hodgkin lymphoma in first complete remission (CR). The 138 PET/CTs performed in 52 patients revealed four unsuspected relapses. In one patient, relapse was visualized by fluorodeoxyglucose (FDG) accumulation without any significant CT pathology. The specificity and sensitivity of surveillance PET/CT were 89% and 100%, respectively. The predictive values of positive and negative PET/CTs were 21% and 100%, respectively. The cost of half-yearly routine PET/CT surveillance during the first 2 years in CR was

Soluble vascular cell adhesion molecule‐1 (sVCAM‐1) is an independent prognostic marker in Hodgkin's disease

US8552 per patient and accounted for 81% of the total follow-up costs. PET/CT was effective in detecting unexpected relapse and normal PET/CT supported continuous CR. However, the impact of PET/CT was limited by the high number of false-positive results and PET/CT surveillance was costly compared to CT surveillance.

Elevated serum levels of soluble vascular cell adhesion molecule‐1 (sVCAM‐1) closely reflect tumour burden in chronic B‐lymphocytic leukaemia

The serum levels of soluble ICAM‐1 (CD54) were significantly elevated in patients with non‐Hodgkin’s lymphomas (NHL, n = 127) and hairy cell leukaemia (HCL, n = 15) compared with healthy controls (n = 31). In high‐grade malignant NHL (n = 79) the sICAM‐1 levels correlated with the tumour mass as reflected in the Ann Arbor staging system but not with bulky disease. Further, the sICAM‐1 levels correlated with disease activity as reflected by the presence of B symptoms and with other known prognostic markers, in particular serum thymidine kinase (sTK). In patients with low‐grade malignant NHL (n = 48) a trend towards higher serum levels of sICAM‐1 was found in patients with advanced stage and B symptoms. In both low‐ and high‐grade malignant NHL, elevated levels of sICAM‐1 were associated with poorer overall and disease‐free survival. The present results indicate that sICAM‐1 levels have a prognostic power equal to that of other serum markers claimed to be of prognostic value in NHL, namely serum lactate dehydrogenase (LDH), erythrocyte sedimentation rate (ESR), beta‐2‐microglobulin (β2m), serum thymidine kinase (sTK), albumin and orosomucoid. The cellular origin and the possible interactions between soluble and surface ICAM‐1 and its ligands needs further exploration.

Soluble ICAM-1 in Hodgkin´s disease : a promising independent predictive marker for survival

Serum levels of soluble vascular cell adhesion molecule‐1 (sVCAM‐1, sCD106) were significantly elevated in patients with Hodgkins disease (HD) (n = 101) compared to controls (n = 31) (P < 0.0001). sVCAM‐1 correlated with histology, stage, B‐symptoms, and prognostic markers (sICAM‐1, sCD30, sIL‐2R, LDH). sVCAM‐1, sICAM‐1 and sCD30 added independent prognostic information for both disease‐free and overall survival. 14 biopsies from 13 patients with HD were immunostained for VCAM‐1 and ICAM‐1. The vascular endothelium stained positive for VCAM‐1 in 10/12 evaluable biopsies and for ICAM‐1 in all evaluable biopsies. A stromal expression of both adhesion molecules precluded a precise evaluation of HRS‐cells. This led us to investigate VCAM‐1 (and ICAM‐1) expression in six Hodgkin cell lines (HDLM‐2, L428, L540, L591, DEV, KM‐H2). Two cell lines stained positive for VCAM‐1 (HDLM‐2, L591). All cell lines stained positive for ICAM‐1. sVCAM‐1 is a new prognostic marker in HD; its predictive power equals or surpasses that of sCD30 and sICAM‐1. Furthermore, two Hodgkin cell lines stained positive for VCAM‐1. This indicates that VCAM‐1 may be expressed by some HD tumour cells in vivo.

CD40 ligation inhibits IL-2 and SAC+IL-2 induced proliferation in chronic lymphocytic leukaemia cells.

The present study is the first to report elevated serum levels of soluble (s)VCAM‐1 in B‐cell chronic lymphocytic leukaemia (B‐CLL). A large cohort of 106 untreated patients was studied. sVCAM‐1 was compared to known prognostic serum markers (soluble (s)ICAM‐1; lactate dehydrogenase, LDH; sCD23; thymidine kinase, TK; β2microglobulin, β2m). The serum levels of sVCAM‐1 reflected tumour burden as expressed by Binet/Rai stages more closely than any other marker. sVCAM‐1 also reflected the kinetics of the disease as revealed by lymphocyte doubling time. sVCAM‐1 was the only one of the studied markers which showed elevated levels in smouldering disease compared to controls. sVCAM‐1, sICAM‐1 and sCD23 (but not LDH, TK, β2m) separated smouldering from non‐smouldering B‐CLL. Only sICAM‐1, sCD23 and TK added independent prognostic information for survival to that of stage and lymphocyte doubling time.