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- Adde, Magdalena, 1960-
(författare)
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Aggressive B-cell Lymphomas : Studies of Treatment, FDG-PET Evaluation and Prognostic Factors
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- To improve outcome in young, high-risk lymphoma patients, treatment was intensified, adding etoposide and rituximab to standard CHOP treatment. Granulocyte-colony stimulating factor (G-CSF) enabled treatment bi-weekly. Results were promising: overall (OS) and event-free survival (EFS) 79% and 60% respectively, median follow up 27 months. Single infusion Ara-C, contrary to expectations, did not prevent relapse in CNS. DLBCL were classified as germinal center (GC) or non-GC derived, using immunohistochemical markers, CD10, BCL6 and MUM1. We investigated the outcome for both phenotypes after adding rituximab to chemotherapy. For 106 patients treated with CHOP alone, the GC phenotype displayed significantly better OS and EFS. In contrast, GC phenotype did not predict outcome in 95 patients treated with immunochemotherapy . Thus, addition of rituximab seems to eliminate the prognostic value of immunohistochemically defined GC phenotypes in DLBCL. To improve evaluation and find non-responders, mid-treatment FDG-PET CT was incorporated into clinical routine for patients with high-risk aggressive lymphoma. For those with positive PET, biopsy followed by treatment intensification was recommended. Twenty-five patients were examined, five with positive PET. Two of these had lymphoma in the biopsy. Two had a negative biopsy, and one had a false positive investigation. Seven patients had increased uptake of uncertain significance. Two patients with uncertain PET, and two with negative PET have relapsed, giving a negative predictive value of 85%. In case of relapse of aggressive lymphoma or if not obtaining CR, high dose chemotherapy with autologous stem cell support (HDT) is standard treatment. HDT outcome for 38 patients with transformed follicular lymphoma was compared to outcome for 79 patients with de novo B-cell lymphoma. At median follow-up of 11.5 years both OS and EFS were superior in the transformed group, OS 67% and 33%, EFS 55% and 27% respectively. Treatment related mortality was less than reported in other studies.
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- Adde, Magdalena, 1960-, et al.
(författare)
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Little usefullness of mid-treatment FDG-PET and biopsy for treatment intensification in patients with aggressive lymphoma
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Purpose: To evaluate the experiences of introducing mid-treatment FDG-PET in patients with aggressive lymphoma, in a population based program with decentralized examinations, with emphasis on finding patients who would benefit from dose-escalation. Patients and Methods: Twenty-five patients with aggressive lymphoma were included. Twenty-four (95%) of these having an aggressive B-cell lymphoma (84% diffuse large B-cell lymphoma) were treated with CHOP-like treatment given at two week intervals + rituximab. One patient having an anaplastic T-cell lymphoma was treated with CHOEP-14. Mid-treatment FDG-PET was performed and assessed as positive, uncertain or negative for remaining lymphoma. The intention was to perform a biopsy in those with a positive FDG-PET, and, to change to a platina-containing therapy and consolidate with high-dose therapy if viable lymphoma was found. Retrospective review of the PET investigations was done. Living patients were followed for a median of 22 months. Results: At primary analysis five patients (20%) had positive uptake on FDG-PET. Two of them had biopsy-proven viable tumor but did not complete the planned salvage treatment, one due to chemotherapy toxicity and one due to progressive disease during salvage therapy. Two patients had a negative biopsy and one patient had no biopsy due to technical difficulties at diagnosis. These three patients remain in remission after standard treatment. Out of seven patients (28%) having “uncertain” uptake two relapsed. Thirteen patients (52%) were negative,two of whom relapsed giving a negative predictive value of 85%. Conclusion: Mid-treatment FDG PET-CT in order to find patients with biopsy-proven aggressive lymphoma, who can be salvaged with dose escalation, was not feasible in clinical routine.
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- Adde, Magdalena, et al.
(författare)
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Superior outcome in transformed follicular lymphoma compared to de novo aggressive B-cell lymphoma treated with high-dose therapy and autologous stem-cell support
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Purpose: To assess the outcome of high–dose therapy with autologous stem cell support (HDT) in patients with transformed follicular lymphoma compared to patients with de novo aggressive B-cell lymphoma, in a retrospective analysis of patients treated at two Swedish university hospitals. Patients and Methods: 117 patients, mean age 48 years (21-65), 79 with de novo aggressive B-cell lymphoma and 38 with transformed follicular lymphoma, were treated with high-dose-therapy (HDT) as consolidation. Thirteen patients with transformed follicular lymphoma had been treated with a single alkylating agent and 25 were chemonaive at transformation. After transformation, nine patients had HDT as part of first line aggressive therapy, and a further eight failed to obtain CR and had HDT upfront. Twenty-one patients received more than one treatment regimen before HDT. In the de novo aggressive lymphoma group five patients with high risk criteria, and 16 patients who failed to obtain CR, received HDT upfront (CR1), Fifty-eight patients received more than one regimen before HDT because of relapse. Rituximab was given as a single dose to five patients for in vivo purging of the stem cell graft. Results: With a median follow up of 11.5 years (8-20), event free survival (EFS) and overall survival (OS) were 35% and 44% respectively. When comparing the two groups, the ten- year EFS rates were 27% in the de novo group and 55% in the transformed group and the ten-year OS was 33 % and 67% respectively. Treatment related mortality was acceptable with 4% early and 3.5% late mortality. In a multivariate analysis, “transformed vs de novo aggressive” histopathology was the only factor significantly related to outcome. Conclusion: Both EFS and OS were much better in patients with transformed follicular lymphoma compared to patients with de novo aggressive B-cell lymphoma Although the introduction of rituximab certainly has improved the outcome in both groups, HDT should still be considered as a salvage strategy not only in cases of de novo aggressive B-cell lymphoma and especially in transformed follicular lymphoma relapsing after first line treatment..
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- Enblad, Gunilla, et al.
(författare)
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A Phase I/IIa Trial Using CD19-Targeted Third-Generation CAR T Cells for Lymphoma and Leukemia
- 2018
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Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 24:24, s. 6185-6194
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The chimeric antigen receptor (CAR) T-cell therapy has been effective for patients with CD19(+) B-cell malignancies. Most studies have investigated the second-generation CARs with either CD28 or 4-1BB costimulatory domains in the CAR receptor. Here, we describe the first clinical phase I/IIa trial using third-generation CAR T cells targeting CD19 to evaluate safety and efficacy.Patients and Methods: Fifteen patients with B-cell lymphoma or leukemia were treated with CAR T cells. The patients with lymphoma received chemotherapy during CAR manufacture and 11 of 15 were given low-dose cyclophosphamide and fludarabine conditioning prior to CAR infusion. Peripheral blood was sampled before and at multiple time points after CAR infusion to evaluate the persistence of CAR T cells and for immune profiling, using quantitative PCR, flow cytometry, and a proteomic array.Results: Treatment with third-generation CAR T cells was generally safe with 4 patients requiring hospitalization due to adverse reactions. Six of the 15 patients had initial complete responses [4/11 lymphoma and 2/4 acute lymphoblastic leukemia (ALL)], and 3 of the patients with lymphoma were in remission at 3 months. Two patients are still alive. Best predictor of response was a good immune status prior to CAR infusion with high IL12, DC-Lamp, Fas ligand, and TRAIL. Responding patients had low monocytic myeloid-derived suppressor cells (MDSCs; CD14(+)CD33(+)HLA(-)DR(-)) and low levels of IL6, IL8, NAP3, sPDL1, and sPDL2.Conclusions: Third-generation CARs may be efficient in patients with advanced B-cell lymphoproliferative malignancy with only modest toxicity. Immune profiling pre- and posttreatment can be used to find response biomarkers.
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