Retraction Note to: Bismuth adjuvant ameliorates adverse effects of high-dose chemotherapy in patients with multiple myeloma and malignant lymphoma undergoing autologous stem cell transplantation: a randomised, double-blind, prospective pilot study.

This article has been retracted. Please see the retraction notice for more detail: https://doi.org/10.1007/s00520-020-05770-w.

Bismuth adjuvant ameliorates adverse effects of high-dose chemotherapy in patients with multiple myeloma and malignant lymphoma undergoing autologous stem cell transplantation: a randomised, double-blind, prospective pilot study.

PURPOSE: High-dose chemotherapy prior to autologous stem cell transplantation (ASCT) leads to adverse effects including mucositis, neutropenia and bacteremia. To reduce the toxicity, we treated myeloma and lymphoma patients with peroral bismuth as an adjuvant to chemotherapy to convey cytoprotection in non-malignant cells. METHODS: This trial was a prospective, randomised, double-blind, placebo-controlled pilot study of hematological inpatients (n = 50) receiving bismuth or placebo tablets, in order to identify any potential superiority of bismuth on toxicity from chemotherapy. RESULTS: We show for the first time that bismuth significantly reduces grade 2 stomatitis, febrile neutropenia and infections caused by melphalan in multiple myeloma, where adverse effects also were significantly linked to gender. In lymphoma patients, bismuth significantly reduces diarrhoea relative to placebo. Also, lymphoma patients' adverse effects were linked to gender. For the first time, bismuth is demonstrated as a safe strategy against chemotherapy's toxicity without interfering with intentional anti-cancer efficiency. Also, we show how gender significantly influences various adverse effects and response to treatment in both multiple myeloma and malignant lymphomas. CONCLUSION: These results may impact clinical prevention of chemotherapy's cytotoxicity in certain patient groups, and also, this study may direct further attention towards the impact of gender during the course and treatment outcome of malignant disorders.

Nordic MCL3 study: 90Y-ibritumomab-tiuxetan added to BEAM/C in non-CR patients before transplant in mantle cell lymphoma.

The main objective of the MCL3 study was to improve outcome for patients not in complete remission (CR) before transplant by adding (90)Y-ibritumomab-tiuxetan (Zevalin) to the high-dose regimen. One hundred sixty untreated, stage II-IV mantle cell lymphoma patients <66 years received rituximab (R)-maxi-CHOP (cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone) alternating with R-high-dose cytarabine (6 cycles total), followed by high-dose BEAM/C (bis-chloroethylnitrosourea, etoposide, cytarabine, and melphalan or cyclophosphamide) and autologous stem cell transplantation from 2005 to 2009. Zevalin (0.4 mCi/kg) was given to responders not in CR before transplant. Overall response rate pretransplant was 97%. The outcome did not differ from that of the historic control: the MCL2 trial with similar treatment except for Zevalin. Overall survival (OS), event-free survival (EFS), and progression-free survival (PFS) at 4 years were 78%, 62%, and 71%, respectively. For responding non-CR patients who received Zevalin, duration of response was shorter than for the CR group. Inferior PFS, EFS, and OS were predicted by positron emission tomography (PET) positivity pretransplant and detectable minimal residual disease (MRD) after transplant. In conclusion, positive PET and MRD were strong predictors of outcome. Intensification with Zevalin may be too late to improve the outcome of patients not in CR before transplant. This trial was registered at www.clinicaltrials.gov as #NCT00514475.

Evaluation of clinical trial eligibility and prognostic indices in a population-based cohort of systemic peripheral T-cell lymphomas from the Danish Lymphoma Registry.

Clinical trials (CTs) are needed to improve the outcome for peripheral T-cell lymphomas (PTCL), and accrual into CTs is one of the main recommendations in international treatment guidelines. The use of risk-adapted strategies has been suggested as a way to optimize treatment outcome in PTCL. The aim of the present study was to evaluate CT eligibility and selected prognostic indices in a population-based PTCL cohort of 481 PTCL patients identified from the Danish Lymphoma Registry in the period 2000-2010. According to five predefined parameters (age, performance status, P-creatinine, P-ALAT and measurable tumour lesion), patients were subdivided into four groups: 'younger fit', 'elderly fit', 'frail' and 'not CT eligible'. International prognostic index (IPI), prognostic index for T-cell lymphoma (PIT) and anaplastic lymphoma kinase (ALK) protein expression were tested at subtype-specific level. Overall, 41% of the patients were considered eligible for interventional CTs implicating curatively intended multiagent chemotherapy, including, if considered appropriate, consolidating stem cell transplantation (SCT), as part of the upfront management strategy. Moreover, 28% was elderly fit and eligible for interventional CT, including those with SCT as part of the trial design. Approximately 7% were defined as 'too frail' for aggressive treatment schedules, whereas 24% were deemed not to be eligible for any CT. Both overall and progression-free survivals were effectively predicted by IPI and PIT (p < 0.001). ALK-positive anaplastic large cell lymphoma patients were significantly younger (median age 40 vs. 62, p < 0.001) and had a better outcome than their ALK-negative counterparts (p < 0.001). However, ALK expression lost its prognostic significance when adjusting for age. In a population-based cohort of adult Caucasian PTCL patients, approximately half were eligible for multiagent chemotherapy with or without consolidating SCT. Both IPI and PIT are useful prognostic indices in all 'primary nodal' PTCL entities. The prognostic value of ALK protein expression in anaplastic large cell lymphoma is significantly downsized when adjusting for age.

Chronic emphysematous osteomyelitis.

Emphysematous osteomyelitis (EO) is a rare and dangerous infection characterized by the presence of intraosseous gas. In this case report, a 65-year-old man with primary central nervous system lymphoma had recurrent infections and pain in his shoulders. Urine and blood cultures revealed Klebsiella pneumoniae. CT showed the formation of gas in the right humerus and left clavicle penetrating the surrounding tissues, which led to the diagnosis of EO. After several long-term antibiotic treatments, the patient underwent surgery on the right proximal humerus. Biopsy cultures revealed K. pneumoniae.

An immunogenic first-in-human immune modulatory vaccine with PD-L1 and PD-L2 peptides is feasible and shows early signs of efficacy in follicular lymphoma.

Cells in the tumor microenvironment of Follicular lymphoma (FL) express checkpoint molecules such as programmed death ligands 1 and 2 (PD-L1 and PD-L2) and are suppressing anti-tumor immune activity. Stimulation of peripheral blood mononuclear cells (PBMC) with PD-L1 (IO103) or PD-L2 (IO120) peptides can activate specific T cells inducing anti-regulatory functions including cytotoxicity against PD-L1/PD-L2-expressing cells. In this study, we vaccinated eight FL patients with PD-L1 and PD-L2 peptides following treatment with standard chemotherapy. Patients experienced grade 1-2 injection site reaction (5/8) and mild flu-like symptoms (6/8). One patient experienced neutropenia and thrombocytopenia during pseudo-progression. Enzyme-linked immunospot detected vaccine-specific immune responses in PBMC from all patients, predominately toward PD-L1. The circulating immune composition was stable during treatment; however, we observed a reduction regulatory T cells, however, not significant. One patient achieved a complete remission during vaccination and two patients had pseudo-progression followed by long-term disease regression. Further examination of these early signs of clinical efficacy of the dual-epitope vaccine in a larger study is warranted.

[A 87-year-old woman was run down by a hit-and-run driver and cured of malignant lymphoma].

A 87-year-old woman was run down by a hit-and-run driver while riding her bicycle. An acute computed tomography (CT) showed no fractures or internal bleedings but revealed an asymptomatic tumour in the colon transversum. During operation, a diffuse large B-cell lymphoma was resected. Subsequent positron emission tomography/CT and bone marrow examination revealed no dissemination. No chemotherapy or radiation therapy was given. The patient was seen in the outpatient clinic every six months, and after two and a half year she is still in complete remission with a normal haemoglobin level.

[Malignant lymphoma complicated with posterior reversible encephalopathy]. / Posterior reversibel encefalopati efterbehandling af malignt lymfom

We present a 56-year-old woman who received chemotherapy for relapsed diffuse large B-cell lymphoma and developed posterior reversible encephalopathy syndrome (PRES) with generalized seizures 27 days after treatment with rituximab, ifosfamide, carboplatin and etoposide (R-ICE). The patient had moderate renal impairment (eGFR > 30 ml/min.) and a normal blood pressure. PRES was confirmed by MRI, which showed oedema of the occipital, parietal and frontal lobes. A control MRI after four weeks showed full remission. To our knowledge this is the first published case of R-ICE causing PRES.

[Pure red cell aplasia developed during treatment with erythropoietin. Complete remission during immunosuppressive therapy]. / Pure red cell-aplasi udviklet under erytropoietinbehandling. Komplet remission under immunosupprimerende terapi.

In a patient with chronic renal failure due to diabetes mellitus pure red-cell aplasia developed during treatment with erythropoietin (epoetin alfa). The treatment with erythropoietin was stopped and immunosuppressive therapy resulted in normalisation of the bone marrow function and increase of the Hb level to normal values. Pure red cell aplasia which develops during treatment with erythropoietin has recently been reported in a few other patients with anaemia due to chronic renal failure. Hitherto our patient is the first case reported in Denmark.

[The myelodysplastic syndrome I. Pathogenesis, clinical symptoms, diagnosis and differential diagnosis]. / Det myelodysplastiske syndrom. I. Patogenese, klinik, diagnostik og differentialdiagnostik.

The myelodysplastic (MDS) syndrome is characterized by variable cytopenia, owing to bone marrow insufficiency. Known provoking factors for the disease are chemicals (benzene), previous treatment with alkylating agents, and radioactive irradiation. The pathogenesis involves an acquired lesion of the pluripotent haematopoietic stem cell with the evolution of a (pre-)malignant cell clone with an increased proliferation potential, but, in addition, severe dysplasia with ineffective haematopoiesis. An increased intramedullary production of various cytokines that inhibit haematopoiesis, including tumour necrosis factor alpha (TNF-alpha), may be responsible for the accelerated cell death (apoptosis). An increasing genetic instability during the course of the disease causes progression of the cytopenia with anaemia, infections, and bleeding. Autoimmune diseases may be seen. The disease often progresses to acute myeloid leukaemia. A chromosomal analysis is important, as 40-50% of the patients have chromosomal changes at the time of diagnosis. Differential diagnostic considerations include temporary dysplasia provoked by medical or toxic agents, B12 or folate deficiency, infectious bone marrow involvement (HIV, CMV infection), chronic alcoholism, aplastic anaemia, and myelofibrosis.

[The myelodysplastic syndrome II. New therapeutic principles, course and prognosis]. / Det myelodysplastiske syndrom. II. Nye behandlingsprincipper, forløb og prognose.

The treatment of the myelodysplastic syndrome (MDS) has formerly been supportive, primarily blood transfusions. Treatment with the growth factor erythropoietin, in combination with granulocyte-colony stimulating factor or granulocyte-macrophage colony stimulating factor is accompanied by a decline in the need for blood transfusions in about 40% of the patients. Likewise, the risk of infections is reduced. Immunosuppressive therapy with cyclosporine and antithymocyte globulin is also capable of improving the cytopenia in about 50% of the patients. Allogeneic bone marrow transplantation is the only possibility of cure in MDS, but the procedure is associated with high mortality. This treatment modality is therefore only recommended for younger patients, who are in a complete remission after being treated for acute myeloid leukaemia or are otherwise in a high risk group. The prognosis is poor, with an overall median survival of about 15 months. A simple scoring system has been elaborated and is based upon the percentage of myeloblasts in the bone marrow, a chromosomal analysis, and the number of cell lines with cytopenia. This system is able to distinguish between three distinct groups of patients with a highly different prognosis (low, intermediate, high risk), which is also of importance when evaluating the best treatment for the individual patient.

[Cerebral aspergillosis in an immunocompromised patient with follicular lymphoma].

We present a case of central nervous system aspergillosis in an immunocompromised 69-year-old male with a history of chemotherapeutic treatment for follicular lymphoma. The patient presented with aphasia, apraxia and confusion. An MRI of the central nervous system and Aspergillus antigen in the spinal fluid was suggestive for this invasive fungal infection. Despite treatment with voriconazole the patient succumbed to the infection. A rise in rare, severe infectious complications as presented is expected due to increasing dose-intensity of chemotherapy.

[Cytomegalovirus-associated haemophagocytic syndrome and acute renal failure in a patient with chronic lymphocytic leukaemia].

A 60-year-old man with chronic lymphocytic leukaemia was admitted to our department with fever and hepatospleno-megaly. Laboratory findings revealed hyperferritinaemia of 40,300 microgram/l and both liver and renal dysfunction. A bone marrow biopsy showed haemophagocytosis consistent with haemophagocytic syndrome. The serology was compatible with acute Cytomegalovirus infection. The patient received therapy with ganciclovir, prednisolone and gamma globulin, and the acute renal failure was treated with haemodialysis. The patient responded well to the treatment and was discharged after a month with normal lever and renal function.

Successful Treatment of Posttransplant EBV-Associated Lymphoma and Plasmacytoma Solely Localized to the CNS.

Two patients with diabetic nephropathy were diagnosed with primary central nervous system posttransplant Epstein-Barr-virus-associated lymphoproliferative disorder (PTLD) 3 years after renal transplantation. The histological diagnoses of the isolated brain tumors were diffuse large B-cell lymphoma and plasmacytoma. Considerable co-morbidity precluded intensive chemotherapy. The first patient with lymphoid CD20+ PTLD had a partial resection of her tumor performed. She was treated with 4 weekly doses of rituximab, ganciclovir and prednisolone; the posttransplant immune suppression (tacrolimus) was reduced. After 4 weeks of treatment a magnetic resonance imaging (MRI) demonstrated complete regression of the CNS lesion. The patient continues to receive rituximab (every second month), valgangciclovir and low-dose prednisolone. Twenty-two months after initiation of therapy, she is still in complete remission. The second patient was only treated with craniospinal irradiation involving the medulla to the second cervical vertebra and valgangciclovir. Moreover, the posttransplant immune suppression was reduced. A new MRI two months after initiation of therapy showed a complete regression of the lesions in the CNS; this was again demonstrated by a MRI after 19 months. These 2 cases illustrate interesting alternative treatments of PTLD. To our knowledge, an EBV-associated PTLD of plasmacytic origin isolated to the CNS has never been described before.

[Indications for radioimmunotherapy for patients with non-Hodgkin's lymphoma]. / Indikationer for radioimmunterapi til patienter med non-Hodgkins lymfom.

Radioimmunotherapy is a well-known treatment for non-Hodgkin's lymphoma. (90)yttrium (Y)-ibritumomab-tiuxetan consists of a radioisotope conjugated to a monoclonal anti-cluster of differentiation 20 antibody, which is targeted against B-lymphocytes. Initially the treatment indication was relapse of low-grade non-Hodgkin's lymphoma. However, (90)Y-ibritumomab-tiuxetan has later been used in clinical trials in the treatment of other types of non-Hodgkin's lymphoma and prior to stem cell transplantation. Based on the literature this systematic review aims to throw light on the future possibilities of radioimmunotherapy.

[Burkitt lymphoma is a highly malign tumour with a doubling time of twenty-four hours]. / Burkitts lymfom er en højmalign tumor med en fordoblingstid på et døgn.

The treatment results for patients with Burkitt lymphoma have improved markedly over the past 20 years. Focus on the rapid doubling time of the lymphoma, and the frequent involvement of the central nervous system, have led to effective intensive chemotherapy regimens, where several of the drugs cross the blood-brain barrier. The overall survival is now 65-80% even when patients have advanced disease at the time of diagnosis. However, the condition and its complications such as tumour lysis syndrome are acute life threatening, and a quick diagnosis and proper management of complications are essential for the prognosis.

[Complete remission of diffuse large B-cell lymphoma of the stomach after eradication of Helicobacter pylori]. / Komplet remission af højmalignt lymfom i ventriklen efter eradikation af Helicobacter pylori.

A 91 year-old man was found to have diffuse large cell B-cell lymphoma (DLBCL), localized to the stomach. Because of his age, his only treatment was anti-Helicobacter pylori therapy. He achieved a complete remission, and six months after the initial presentation, there were no signs of recurrence. The recommended treatment of DLBCL is chemotherapy followed by involved-field irradiation. However, small prospective trials have shown high rates of complete remission after eradication of H. pylori alone and this treatment is an option in patients of advanced age or with severe co-morbidities.

[Treatment of central nervous system lymphoma following transplantation using monoclonal antibody and ganciclovir]. / Behandling af centralnervesystemlymfom efter transplantation med monoklonalt antistof og ganciclovir.

A 35-year-old female was diagnosed with a primary central nervous system posttransplant Epstein-Barr-virus-associated lymphoproliferative disorder three years after a renal transplantation. The histological diagnosis of the brain tumour was a diffuse large B-cell lymphoma. The patient had had diabetes mellitus for 28 years and was treated with four weekly doses of the monoclonal antibody rituximab, the antiviral drug ganciclovir and high-dose prednisolone, and the immune suppression was reduced. After four weeks of treatment, a control magnetic resonance image showed complete regression of the central nervous system lesion.

[Mobilisation of haematopoietic stem cells with plerixafor--secondary publication]. / Mobilisering af haematopoietiske stamceller med plerixafor--sekundaerpublikation.

Plerixafor (AMD3100) is a selective antagonist of a receptor expressed on haematopoietic stem cells. This receptor normally binds to a ligand on bone marrow stromal cells, responsible for the homing and keeping the stem cells in place. Plerixafor has been successfully used in clinical trails in patients with malignant lymphoma and multiple myeloma, where mobilization of stem cells with granulocyte colony-stimulating factor for leukapheresis and later stem cell transplantation were not possible. Plerixafor has also been given with success to healthy donors for harvest and haematopoietic allograft.