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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.

Issue Title: Including PIH Articles on How to improve the outcome of adult acute myeloid leukemia?

Blood group incompatibility between donor and recipient of allogeneic stem cell transplants may be associated with post-transplant erythroid aplasia. A total of 548 patients (pts) received allogeneic transplant for malignant and non-malignant hematologic disorders. In a retrospective analysis, the prevalence and outcome of pure red-cell aplasia (PRCA) in 44 pts with major and bi-directional ABO-mismatch were investigated. Bone marrow grafts were major ABO incompatible in 30 pts; there was bi-directional mismatch in the remaining 14 pts. The median number of transplanted mononuclear cells (NC) was 4.74 x 10(8)/kg (range 0.1-26.4) including CD34+ cells, 3.02 x 10(6)/kg (range 0.9-21.7). Granulocyte engraftment >0.5 x 10e9/l occurred after a median of 21 days (7-32), and platelet exceeded >50 x 10e9/l after a median of 23.5 days (12-109). Acute and chronic graft vs host disease (GVHD) developed in 23 (52%) and 26 (59%) of the patients, respectively. Six (13%) patients transplanted with major and bi-directional ABO-incompatibility developed PRCA. The treatment of PRCA consisted of plasmapheresis (PEX), rapid cyclosporine (CsA) discontinuation, donor lymphocyte infusions (DLI), erythropoietin (EPO), azathioprine, and rituximab. The therapy resulted in erythroid recovery in five out of six patients after a median of 13 months (range 3-16). The median number of transfused red blood cells (RBCs) was 36 U (range 8-57). With a median follow-up of 37 months, the 5-year probability of overall survival (OS) for the PRCA group was 66%. Major ABO mismatch may lead to delayed donor erythroid engraftment. It results in long-term transfusion dependence and, therefore, the risk of iron overload. The therapy is long lasting, but usually effective in majority of patients.

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.

Between January 2017 and July 2018 103 patients were included in a prospective study of erythropoietin (EPO) monitoring. The group consisted of 33% patients with oropharynx, 29% with oral cavity, 13% with nasopharynx, 6% with larynx, 6% with hypopharynx, 8% with unknown primary cancer, 4% with nasal cavity, and 1% with salivary gland cancer. Clinic stage: T4 – 50, T3 – 21, T2 – 14, T1 – 10, T0 – 8, and N3 – 19, N2 – 61, N1 – 10, N0 – 13. All patients received from one to four cycles of induction chemotherapy. EPO was measured in blood serum by enzyme-labelled chemiluminescent immunometric assay, using an Immulite 2000XPi analyser before the administration and on day 11 of each chemotherapy cycle. During induction chemotherapy the EPO level was elevated in all patients, which is expressed by means of medians: 10.7 (p = 0.000001) in the middle of cycle 1; 10.9 (p = 0.66) before cycle 2; 14.35 (p = 0.000177) in the middle of cycle 2; 14.95 (p = 0.39) before cycle 3, 17.00 (p = 0.00078) in the middle of cycle 3, and 20.9 after cycle 3 (p = 0.41). The correlation analysis conducted indicates that the administration of one chemotherapy dose results in higher EPO release (two-fold increase in EPO concentration) which intensifies reticulocytes (REC) production but without haemoglobin concentration in reticulocytes (HGB-REC) growth. In consequence, it leads to a decrease in RBC and HGB concentration (29–32 cases). The administration of two and three chemotherapy doses results in the subsequent higher release of EPO, which does not intensify REC production. In consequence, anaemia increases (35 cases).

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.

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.