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      The Karolinska experience of autologous stem-cell transplantation for lymphoma: a population-based study of all 433 patients 1994–2016

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          Abstract

          Background

          Autologous stem-cell transplantation (ASCT) is a common treatment for lymphoma but it has some mortality.

          Methods

          All 433 lymphoma patients who underwent ASCT for lymphoma at Karolinska Huddinge 1994–2016 were investigated, including CD34 + cell amounts, medications, infectious and other complications, intensive care, longitudinal laboratory values, and secondary myeloid neoplasia.

          Results

          The 100-day non-relapse and overall mortalities were 5.6% and 7.2%. Stem-cell harvests < 5 million CD34 + cells/kg correlated with inferior 100-day and long-term survival. Prior to conditioning (93% BEAM), elevated (both 3–9 and ≥ 10 mg/L) C-reactive protein (CRP) and creatinine, and low albumin (but not higher age) predicted inferior higher 100-day survival. Intravenous antibiotics were given to 97% (22% positive blood cultures) and parenteral nutrition to 89%. After 1 year, 86% had normalized hemoglobin. The 5-year risk for secondary myeloid neoplasia was 4.1%, associated with smaller harvests.

          Conclusions

          Before starting conditioning, patients should have preferably harvested ≥ 5 million CD34 + cells/kg and normal CRP, albumin, and creatinine. It appears safe to transplant patients ≥ 66 years.

          Electronic supplementary material

          The online version of this article (10.1186/s40164-019-0131-3) contains supplementary material, which is available to authorized users.

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          Most cited references30

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          Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma.

          High-dose chemotherapy followed by autologous bone marrow transplantation is a therapeutic option for patients with chemotherapy-sensitive non-Hodgkin's lymphoma who have relapses. In this report we describe a prospective randomized study of such treatment. A total of 215 patients with relapses of non-Hodgkin's lymphoma were treated between July 1987 and June 1994. All patients received two courses of conventional chemotherapy. The 109 patients who had a response to chemotherapy were randomly assigned to receive four courses of chemotherapy plus radiotherapy (54 patients) or radiotherapy plus intensive chemotherapy and autologous bone marrow transplantation (55 patients). The overall rate of response to conventional chemotherapy was 58 percent; among patients with relapses after chemotherapy, the response rate was 64 percent, and among those with relapses during chemotherapy, the response rate was 21 percent. There were three deaths from toxic effects among the patients in the transplantation group, and none among those in the group receiving chemotherapy without transplantation. The two groups did not differ in terms of prognostic factors. The median follow-up time was 63 months. The response rate was 84 percent after bone marrow transplantation and 44 percent after chemotherapy without transplantation. At five years, the rate of event-free survival was 46 percent in the transplantation group and 12 percent in the group receiving chemotherapy without transplantation (P = 0.001), and the rate of overall survival was 53 and 32 percent, respectively (P = 0.038). As compared with conventional chemotherapy, treatment with high-dose chemotherapy and autologous bone marrow transplantation increases event-free and overall survival in patients with chemotherapy-sensitive non-Hodgkin's lymphoma in relapse.
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            Dose intensification with autologous bone-marrow transplantation in relapsed and resistant Hodgkin's disease: results of a BNLI randomised trial.

            High-dose chemotherapy and radiotherapy with autologous bone-marrow transplantation (ABMT) are increasingly used for the treatment of relapsed and resistant Hodgkin's disease, although there has been no randomised trial of this treatment. The British National Lymphoma Investigation therefore undertook a randomised comparison of high-dose chemotherapy (BEAM = carmustine, etoposide, cytarabine, and melphalan) plus ABMT with the same drugs at lower doses not requiring bone-marrow rescue (mini-BEAM) in patients with active Hodgkin's disease, for whom conventional therapy had failed. 20 patients were assigned treatment with BEAM plus ABMT and 20 mini-BEAM. All have been followed up for at least 12 months (median 34 months). 5 BEAM recipients have died (2 from causes related to ABMT and 3 from disease progression) compared with 9 mini-BEAM recipients (all disease progression). This difference was not significant (p = 0.318). However, both event-free survival and progression-free survival showed significant differences in favour of BEAM plus ABMT (p = 0.025 and p = 0.005, respectively). Recruitment to the trial became increasingly difficult because patients refused randomisation and requested ABMT. It was therefore closed early (40 patients rather than 66 intended). Nevertheless, we found a dose-response effect in these patients with relapsed and resistant Hodgkin's disease. High doses facilitated by ABMT can lead to better disease-free survival.
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              Long-term progression-free survival of mantle cell lymphoma after intensive front-line immunochemotherapy with in vivo-purged stem cell rescue: a nonrandomized phase 2 multicenter study by the Nordic Lymphoma Group.

              Mantle cell lymphoma (MCL) is considered incurable. Intensive immunochemotherapy with stem cell support has not been tested in large, prospective series. In the 2nd Nordic MCL trial, we treated 160 consecutive, untreated patients younger than 66 years in a phase 2 protocol with dose-intensified induction immunochemotherapy with rituximab (R) + cyclophosphamide, vincristine, doxorubicin, prednisone (maxi-CHOP), alternating with R + high-dose cytarabine. Responders received high-dose chemotherapy with BEAM or BEAC (carmustine, etoposide, cytarabine, and melphalan/cyclophosphamide) with R-in vivo purged autologous stem cell support. Overall and complete response was achieved in 96% and 54%, respectively. The 6-year overall, event-free, and progression-free survival were 70%, 56%, and 66%, respectively, with no relapses occurring after 5 years. Multivariate analysis showed Ki-67 to be the sole independent predictor of event-free survival. The nonrelapse mortality was 5%. The majority of stem cell products and patients assessed with polymerase chain reaction (PCR) after transplantation were negative. Compared with our historical control, the Nordic MCL-1 trial, the event-free, overall, and progression-free survival, the duration of molecular remission, and the proportion of PCR-negative stem cell products were significantly increased (P < .001). Intensive immunochemotherapy with in vivo purged stem cell support can lead to long-term progression-free survival of MCL and perhaps cure. Registered at www.isrctn.org as #ISRCTN 87866680.
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                Author and article information

                Contributors
                bjorn.wahlin@ki.se
                Journal
                Exp Hematol Oncol
                Exp Hematol Oncol
                Experimental Hematology & Oncology
                BioMed Central (London )
                2162-3619
                18 March 2019
                18 March 2019
                2019
                : 8
                : 7
                Affiliations
                [1 ]ISNI 0000 0004 1937 0626, GRID grid.4714.6, Center for Hematology and Regenerative Medicine, Dept. of Medicine, Huddinge, , Karolinska Institutet, ; Stockholm, Sweden
                [2 ]ISNI 0000 0000 9241 5705, GRID grid.24381.3c, PO Hematology, , Karolinska University Hospital, ; Stockholm, Sweden
                [3 ]ISNI 0000 0004 1937 0626, GRID grid.4714.6, Division of Clinical Chemistry, Dept. of Laboratory Medicine, , H5, Karolinska Institutet, ; Stockholm, Sweden
                [4 ]ISNI 0000 0004 1937 0626, GRID grid.4714.6, Division of Hematology, Dept. of Medicine, Huddinge, , Karolinska Institutet, ; Stockholm, Sweden
                [5 ]ISNI 0000 0000 9241 5705, GRID grid.24381.3c, Dept. of Cellular Therapy and Allogeneic Stem Cell Transplantation, , Karolinska University Hospital, ; Stockholm, Sweden
                Author information
                http://orcid.org/0000-0003-3566-8847
                Article
                131
                10.1186/s40164-019-0131-3
                6423752
                f943e4f8-dd8b-4ad3-bec5-e523b117c331
                © The Author(s) 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 11 February 2019
                : 13 March 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100002794, Cancerfonden;
                Funded by: FundRef http://dx.doi.org/10.13039/501100003748, Svenska Sällskapet för Medicinsk Forskning;
                Funded by: FundRef http://dx.doi.org/10.13039/501100004348, Stockholms Läns Landsting;
                Categories
                Research
                Custom metadata
                © The Author(s) 2019

                Oncology & Radiotherapy
                autologous stem cell transplantation,asct,beam,lymphoma,real-world,survival
                Oncology & Radiotherapy
                autologous stem cell transplantation, asct, beam, lymphoma, real-world, survival

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