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Background: The aim of this study was to investigate dosimetry data and clinical variables to predict hematological toxicity in non-Hodgkin lymphoma (NHL) patients treated with [177Lutetium]Lu-liloto-mab satetraxetan. Material and methods: A total of 17 patients treated with [177Lu]Lu-lilotomab satetraxetan in a first-in-human phase 1/2a study were included. Absorbed dose to the red marrow was explored using SPECT/CT-imaging of the lumbar vertebrae L2–L4 over multiple time points. Percentage reduction of thrombocytes and neutrophils at nadir compared to baseline (PBN) and time to nadir (TTN) were chosen as indicators of myelosuppression and included as dependent variables. Two models were applied in the analysis, a multivariate linear model and a sigmoidal description of toxicity as a function of absorbed dose. A total of 10 independent patient variables were investigated in the multivariate analysis. Results: Absorbed dose to the red marrow ranged from 1 to 4 Gy. Absorbed dose to the red marrow was found to be the only significant variable for PBN for both thrombocytes and neutrophils. The sigmoid function gave similar results in terms of accuracy when compared to the linear model. Conclusion: Myelosuppression in the form of thrombocytopenia and neutropenia in patients treated with [177Lu]Lu-lilotomab satetraxetan can be predicted from the SPECT/CT-derived absorbed dose estimate to the red marrow. The present work was financially supported by the South-Eastern Norway Regional Health Authority.

Recommended treatment for lymphoblastic lymphomas, a highly aggressive, relatively rare lymphoma entity predominantly seen in teenagers and young adults, includes acute lymphoblastic leukemia (ALL)-like induction chemotherapy. Whether these patients should be consolidated with maintenance chemotherapy or autologous stem cell transplantation (Auto-SCT) and the use of radiotherapy are matters of debate.We reviewed treatment and outcome for 25 consecutive patients above the age of 15 years with lymphoblastic lymphoma (T-lineage; T-LBL, n = 19; B-lineage; B-LBL, n = 6) seen at a single center during a 12-year period (1999-2011). Patients were given an ALL-like chemotherapy induction regimen, and responding patients were consolidated with Auto-SCT and local radiotherapy when applicable.Median age at diagnosis was 33 years (range 15-65). Seventeen of the T-LBL patients had a mediastinal mass, three patients had central nervous system (CNS) involvement. Chemotherapy with intensified CNS prophylaxis induced an overall response rate of 92% (CR 84%, PR 8%). In total 23/25 (92%) patients underwent Auto-SCT in first remission while 13 of 14 eligible patients with mediastinal involvement received local radiotherapy. Twenty percent of the patients had hepatotoxicity grade 3-4 and 32% thromboembolic events (TE). Two patients (8%) died of treatment-related toxicity. One patient had progressive disease and died of lymphoma. Three patients have relapsed, but two of these (both B-LBL) are currently alive in second CR after Allo-SCT. With a median follow-up of 98 months (range 1-163) the 5- and 8-year PFS and OS are 76% and 84%, respectively.Combined intensive ALL-like induction and early consolidation chemotherapy followed by Auto-SCT and local radiation therapy resulted in high sustained cure rates.

MCL is a rare entity of non-Hodgkin lymphoma, hitherto considered incurable. There is no standard therapy, but the current treatment results do seem to have led to a prolongation of the median survival from 3 to 5 years. Following CHOP-like induction, high-dose radiochemotherapy, and autologous stem cell transplantation (ASCT) chemotherapy has been shown in a controlled trial to be superior in younger patients, but does not, however, lead to long-term freedom from disease. Results of recent prospective but uncontrolled trials of more intensive frontline immunochemotherapy containing cytarabine and rituximab followed by ASCT, however, now for the first time indicate plateaus of the curves of event-free, progression-free and overall survival, suggesting cure, but more studies and longer follow-up is needed. Following relapse, autologous stem-cell transplantation does not seem to be of value, but graft-versus-lymphoma effect has been documented, and allogeneic stem cell transplantation with reduced-intensity conditioning is emerging as the treatment of choice in this setting.

There is no consensus on the optimal chemotherapy regimen for Hodgkin's lymphoma patients > or = 60 years. We present our institution's results of 5 years, using CHOP-21 as standard for this patient group. Twenty-nine patients with a median age of 71 years (range, 60 - 91) were included in this cohort. Fifty-five percent had known co-morbidities. Stage I/IIA patients (38%) were treated with 2 - 4 cycles of CHOP followed by radiotherapy. Stage IIB - IV patients (62%) received 6 - 8 cycles of CHOP and for the majority (13/18 pts) no radiotherapy. Two treatment-related deaths occurred. Febrile neutropenia was the most common toxicity (31%). The complete response rate after CHOP +/- radiotherapy was 93%. With a median follow-up of 41 months, five patients have relapsed and four have died from Hodgkin's lymphoma. So far, no relapses have occurred after 2 years from the end of therapy. Overall survival and progression-free survival at 3 years were 79% and 76%, respectively. We conclude that CHOP-21 is a well-tolerated and effective treatment for elderly patients with Hodgkin's lymphoma.

The Nordic Lymphoma Group Mantle Cell Lymphoma 5 trial (MCL5) was launched in 2011 (EudraCT 2011-001557-85), aimed to improve the outcome of younger patients with MCL with high Mantle Cell Lymphoma...

The purpose of this study was to investigate the relationship between the use of alternative medicine (AM) by cancer patients' and the level of self-perceived mental distress. One hundred and fifty-seven cancer patients were included in a longitudinal questionnaire-based study 12 months after their first contact with the Department of Oncology, University Hospital of Tromsø, during the period 1990 to 1991. Eligible patients received follow-up questionnaires after 24 and 60 months recording their use of AM and measuring their perceived mental distress (GHQ-20). A total of 64 (41%) of the 157 patients who completed at least one questionnaire reported using AM one or more times during follow-up (ever-use). Between 65% and 79% of patients who were eligible at each point of the study completed the GHQ questionnaire. After 60 months of follow-up, 104 patients were still alive and 54 patients (52% of the survivors) had completed all the questionnaires. At inclusion in the study, significantly more AM users reported mental distress (57%) than non-users (20%) (p = 0.001). After 24 and 60 months, the corresponding figures were 42% versus 29% (p = 0.18), and 30% versus 10% (p = 0.02), respectively. When adjusted for sex, age and disease progression, use of AM was found to be an independent factor highly associated with mental distress at 12 months (OR = 5.5, 95% CI 2.1-14.4). Later in the study, progression/relapse of cancer proved to be a more important predictor of mental distress. These findings suggest that, in North Norway, seeking alternative treatment is more common among mentally distressed cancer patients.

T cells engineered to express chimeric antigen receptors (CARs) targeted to CD19 are effective in treatment of B-lymphoid malignancies. However, CARs recognize all CD19 positive (pos) cells, and durable responses are linked to profound depletion of normal B cells. Here, we designed a strategy to specifically target patient B cells by utilizing the fact that T-cell receptors (TCRs), in contrast to CARs, are restricted by HLA. Two TCRs recognizing a peptide from CD20 (SLFLGILSV) in the context of foreign HLA-A*02:01 (CD20p/HLA-A2) were expressed as 2A-bicistronic constructs. T cells re-directed with the A23 and A94 TCR constructs efficiently recognized malignant HLA-A2(pos) B cells endogenously expressing CD20, including patient-derived follicular lymphoma and chronic lymphocytic leukemia (CLL) cells. In contrast, a wide range of HLA-A2(pos)CD20(neg) cells representing different tissue origins, and HLA-A2(neg)CD20(pos) cells, were not recognized. Cytotoxic T cells re-directed with CD20p/HLA-A2-specific TCRs or CD19 CARs responded with similar potencies to cells endogenously expressing comparable levels of CD20 and CD19. The CD20p/HLA-A2-specific TCRs recognized CD20p bound to HLA-A2 with high functional avidity. The results show that T cells expressing CD20p/HLA-A2-specific TCRs efficiently and specifically target B cells. When used in context of an HLA-haploidentical allogeneic stem cell transplantation where the donor is HLA-A2(neg) and the patient HLA-A2(pos), these T cells would selectively kill patient-derived B cells and allow reconstitution of the B-cell compartment with HLA-A2(neg) donor cells. These results should pave the way for clinical testing of T cells genetically engineered to target malignant B cells without permanent depletion of normal B cells.