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The goal of this phase II trial was to evaluate safety and efficacy of a tandem autologous hematopoietic cell transplantation (auto-HCT) using sequentially total marrow irradiation (TMI) at the dose of 12 Gy (4 Gy on days −3, −2, and −1) and melphalan 200 mg/m2 for patients with multiple myeloma (MM). TMI was performed using helical tomotherapy. Additional “boosts” (total 24 Gy) were applied for patients with active lesions as revealed by PET-FDG. Fifty patients with median age 58 years (41–64 years) were included and received tandem auto-HCT. TMI resulted in absolute neutropenia in all patients. Grade 3 infections were reported in 30% patients. Other toxicities were rare. Proportion of patients who achieved at least very good partial response increased from 46% before the first auto-HCT to 82% after tandem transplantation. Complete remission rates changed from 10% to 42%, respectively. The probabilities of overall and progression-free survival at 5 years were 74% and 55%, respectively. No patient died without progression. We conclude that conditioning with TMI ± PET-guided “boosts” represents personalized treatment approach in MM and is characterized by very good toxicity profile. Tandem auto-HCT using TMI in sequence with high-dose melphalan appears safe with encouraging early efficacy.

The optimal salvage therapy in relapsed/refractory Hodgkin lymphoma (R/R HL) has not been defined so far. The goal of this multicenter retrospective study was to evaluate efficacy and safety of BGD (bendamustine, gemcitabine, dexamethasone) as a second or subsequent line of therapy in classical R/R HL. We have evaluated 92 consecutive R/R HL patients treated with BGD. Median age was 34.5 (19–82) years. Fifty-eight patients (63%) had received 2 or more lines of chemotherapy, 32 patients (34.8%) radiotherapy, and 21 patients (22.8%) an autologous hematopoietic stem cell transplantation (autoHCT). Forty-four patients (47.8%) were resistant to first line of chemotherapy. BGD therapy consisted of bendamustine 90 mg/m2 on days 1 and 2, gemcitabine 800 mg/m2 on days 1 and 4, dexamethasone 40 mg on days 1–4. Median number of BGD cycles was 4 (2–7). The following adverse events ≥ 3 grade were noted: neutropenia (22.8%), thrombocytopenia (20.7%), anemia (15.2%), infections (10.9%), AST/ALT increase (2.2%), and skin rush (1.1%). After BGD therapy, 51 (55.4%) patients achieved complete remission, 23 (25%)—partial response, 7 (7.6%)—stable disease, and 11 (12%) patients experienced progression disease. AutoHCT was conducted in 42 (45.7%) patients after BGD therapy, and allogeneic HCT (alloHCT) in 16 (17.4%) patients. Median progression-free survival was 21 months. BGD is a highly effective, well-tolerated salvage regimen for patients with R/R HL, providing an excellent bridge to auto- or alloHCT.

Introduction BEAM (carmustine, etoposide, cytarabine, melphalan) is the most frequently used high-dose chemotherapy regimen for patients with lymphoma referred for autologous haematopoietic cell transplantation (autoHCT). Recently, a novel conditioning protocol containing bendamustine instead of carmustine (BeEAM) has been proposed to potentially increase the efficacy. Aim of the study The aim of this study was to retrospectively compare the safety profile of BEAM and BeEAM based on single-centre experience. Material and methods A total of 237 consecutive patients with lymphoma treated with either BEAM (n = 174) or BeEAM (n = 63), between the years 2011 and 2016, were included in the analysis. Clinical characteristics of both groups were comparable. Patients with Hodgkin’s lymphoma (HL) constituted 49% of the BEAM group and 40% of the BeEAM group. Results Median time to neutrophil > 0.5 × 109/l recovery was 10 days in both groups (p = 0.29), while median time to platelet > 50 ×109/l recovery was 13 and 14 days after BEAM and BeEAM, respectively (p = 0.12). The toxicity profile was comparable except for arterial hypertension and severe hypokalaemia, which occurred more frequently after BeEAM compared to BEAM (p = 0.02 and p = 0.004, respectively). The rate of early mortality was 1.7% and 1.6%, respectively. The probabilities of the overall and progression-free survival were comparable for both groups (p = 0.73 and p = 0.55, respectively). Conclusions Administration of bendamustine instead of carmustine as part of conditioning does not affect the engraftment or the toxicity profile of the regimen. Therefore, BeEAM may be safely used in patients with lymphoma undergoing autoHCT. Its efficacy requires evaluation in prospective studies.

Introduction Progress in the transplant procedure has resulted in a higher proportion of patients with long-term survival after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Cutaneous graft-versus-host disease (GvHD) occurs often among patients who have undergone allo-HSCT. Routine diagnosis of skin and mucosal lesions is based primarily on clinical evaluation and histopathologic confirmation of skin biopsies. However, biopsy is an invasive method and histopathologic analysis is time-consuming, often accompanied by a lack of clinical correlation. There is therefore an urgent need for non-invasive, reproducible in vivo imaging methods that could be used in patients with cutaneous GvHD—both in the setting of initial diagnosis and during follow-up.The aim of the study reported here was to determine the role of dermoscopic monitoring of skin lesions in allo-HSCT recipients with consecutive histopathologic support as a non-invasive, alternative method to diagnose GvHD. Methods Twenty patients were examined by dermoscopy upon the manifestation of skin changes in the course of GvHD. Consecutive skin biopsies for histopathologic analysis were obtained from the suspected skin locations determined during dermoscopy. Results Graft-versus-host disease was confirmed by histopathology in 19 of the 20 allo-HSCT recipients. Four patients developed symptoms of acute cutaneous GvHD (grade 1, n  = 2; grade 2, n  = 1; grade 3, n  = 1), and 15 patients developed chronic cutaneous GvHD. The most frequent dermoscopic signs (irrespective of whether GvHD was chronic or acute) were vessels and scaling (both n  = 14, 73.7%). Hyperpigmentation and white patchy areas were present in eight patients (42.1%). Fair to moderate levels of agreement were found between presence of melanophages in the skin sample and dermoscopic granularity (Cohen’s Kappa [ κ ] = 0.39), scaling ( κ  = − 0.3) and vessels ( κ  = − 0.42). The finding of white patchy areas was inversely associated with lymphocytic infiltration ( κ  = − 0.55). Conclusion The results of this study suggest that dermoscopy may be a useful tool for diagnosing cutaneous GvHD in allo-HSCT recipients. Combining the clinical picture with dermoscopic features may bring us closer to a faster and easier diagnosis of GvHD.

The procedure of autologous peripheral blood stem cell transplantation (autoPBSCT) requires cryopreservation of cells in a mixture containing dimethyl sulfoxide (DMSO). DMSO is necessary to secure cell viability, however, its infusion may be toxic to stem cell recipient. The aim of this study was to prospectively evaluate the impact of DMSO concentration on engraftment after autoPBSCT. One-hundred-fifty patients were randomly assigned to one of three study arms; their leukapheresis products were cryopreserved in 10%, 7.5% or 5% DMSO. The study groups did not differ with regard to the diagnosis (mainly lymphomas and multiple myeloma), age, conditioning regimen, and the number of transplanted hematopoietic stem cells. 143 patients were treated with autoPBSCT. The frequency of adverse effects during and shortly after infusion was the lowest in 5% DMSO arm ( p  = 0.02 compared to 10% DMSO). 4 patients died due to infection before the engraftment. The median time to leukocyte and neutrophil recovery was 10 days in all study groups ( p  = 0.36 and p  = 0.2). As well, the median day of platelet recovery was the same for all DMSO concentrations and equaled 15 days ( p  = 0.61). In view of these results, 5% DMSO mixture may be considered a new standard in cryopreservation of hematopoietic stem cells.

A Correction to this paper has been published: https://doi.org/10.1007/s00277-021-04503-1

Salvage regimens, like DHAP (dexamethasone, cytarabine, and cisplatin) are frequently used for stem cell mobilization in lymphoma. The aim of this study was to compare the efficacy of DHAP + G-CSF with intermediate-dose cytarabine (ID-AraC) + G-CSF, recently proposed as an alternative schedule. Consecutive patients with Hodgkin’s or non-Hodgkin lymphoma who had received at least 2 lines of chemotherapy, mobilized with either DHAP ( n  = 51) or ID-AraC ( n  = 50) + G-CSF were included in the analysis. AraC was administered at the dose of 400 mg/m [ 1 ] bid intravenously for 2 days followed by filgrastim starting from day 5. In the AraC group, 96 % of patients collected at least 2 × 10 [ 2 ] CD34 + cells/kg compared to 71 % in the DHAP group ( p  = 0.0006). The CD34 + cell yield was 9.3 (0–30.3) × 10 [ 2 ]/kg vs. 5.6 (0–24.8) × 10 [ 2 ]/kg, respectively ( p  = 0.006). A single apheresis was sufficient to achieve the threshold number of CD34 + cells in 82 % of the cases after AraC compared to 45 % after DHAP ( p  = 0.001). We conclude that stem cell mobilization using ID-AraC is associated with a significantly higher efficacy than DHAP, allowing for collection of the transplant material in almost all patients with lymphoma. Our observation suggests that ID-AraC + G-CSF may be a preferable mobilization regimen in this setting.

Introduction: JAK2V617F, a point mutation involving the JAK2 tyrosine kinase gene, occurs in nearly all patients with polycythaemia vera (PV) and in a variable subset of patients with other myeloproliferative neoplasms (MPN). Aim: We addressed the issue of whe-ther the presence of JAK2 V617F correlates with clinical phenotype. Material and methods: In a single institution study we screened for the JAK2 point mutation in 60 consecutive patients with PV and essential thrombocythaemia (ET). The mutation was detected in peripheral blood granulocyte DNA using allelic discrimination polymerase chain reac-tion (PCR). Results: In total, 42 (70%) patients were positive for this mutation, including 21 subjects with PV (100%), and 21 with TE (54%). The frequency of homozygosity was 21% in PV patients and 0% in ET patients. We found no difference in age at diagnosis, gender or disease duration between patients with and without the mutation. However, a significantly higher haemoglobin concentration and white blood cell count were observed in cases with the JAK2 point mutation. Conversely, the platelet count was significantly lower in V617F-positive cases. Thrombotic complications were more common in patients with V617F. Conclusions: Our results support the previous observation that JAK2 point mutation is associated with some clinical and haematological features in patients with PV and ET.