Pavel Žák

Pre-transplant positron emission tomography in patients with relapsed Hodgkin lymphoma

This retrospective study evaluated the secondary clinical risk score at relapse, the prognostic significance of pre-transplant positron emission tomography (PET), and complete remission (CR) assessed by computed tomography (CT) after salvage chemotherapy before autologous stem cell transplant (ASCT) in 76 patients with relapsed/refractory Hodgkin lymphoma (HL). Median follow-up after ASCT was 23 months. Overall 11/20 PET-positive and 14/56 PET-negative patients relapsed after ASCT. In univariate analysis, only PET negativity before ASCT was significantly associated with better 2-year progression-free survival (PFS) (72.7 ± 6.3% vs. 36.1 ± 11.6%, p = 0.01) and 2-year overall survival (OS) (90.3 ± 4.1% vs. 61.4 ± 11.6%, p = 0.009). Other factors were not significant. In multivariate analysis, none of the evaluated factors were significant for PFS and OS. However, positive pre-transplant PET identified a population with worse PFS and OS at least in univariate analysis.

Venous thromboembolism in patients with chronic lymphocytic leukemia

INTRODUCTION Venous thromboembolism (VTE) is a major cause of morbidity and mortality in patients (pts) with malignant tumors. Increased risk of VTE is well described in a variety of hematologic malignancies; however, data regarding VTE in chronic lymphocytic leukemia (CLL) is very limited. PATIENTS AND METHODS We retrospectively analyzed clinical and laboratory data of 346 consecutive pts with CLL followed up at 4th Department of Internal Medicine - Hematology, University Hospital, Hradec Kralove, Czech Republic, diagnosed between 1999 and 2011 (males, 64%; median age, 64 years; low/intermediate/high Rai modified risk in 41/47/12%). RESULTS After a median follow-up of 72 months (range, 26-138), at least one episode of VTE occurred in 38 patients (11%). VTE developed after a median of 34 months from CLL diagnosis. Incidence of VTE was 1.67% per patient year of follow-up. There was a high proportion of unfavourable prognostic factors (advanced Rai stages, unmutated IgVH genes, unfavourable cytogenetics) in pts with VTE. The presence of 0/1/2/3 additional risk factors for VTE was identified in 2/16/14/6 patients. The most common risk factors for VTE besides age (n=24) were corticosteroid therapy (n=13), other malignancies (n=9) and obesity (n=7). Recurrence of VTE was diagnosed in 7 pts. Performance status ≥ 2 and inherited thrombophilia were significant risk factors for VTE development in univariate and multivariate analysis. VTE was not associated with shorter overall survival. CONCLUSION Based on our results, VTE is a relatively frequent complication in patients with CLL. Although most patients had other known risk factors for VTE including CLL treatment, 29% had no risk factors or only age ≥ 60 years. These findings demonstrate the possible role of CLL in the development of VTE.

Characteristics and outcome of patients with therapy-related acute promyelocytic leukemia front-line treated with or without arsenic trioxide

Therapy-related acute promyelocytic leukemia (t-APL) is relatively rare, with limited data on outcome after treatment with arsenic trioxide (ATO) compared to standard intensive chemotherapy (CTX). We evaluated 103 adult t-APL patients undergoing treatment with all-trans retinoic acid (ATRA) alone (n=7) or in combination with ATO (n=24), CTX (n=53), or both (n=19). Complete remissions were achieved after induction therapy in 57% with ATRA, 100% with ATO/ATRA, 78% with CTX/ATRA, and 95% with CTX/ATO/ATRA. Early death rates were 43% for ATRA, 0% for ATO/ATRA, 12% for CTX/ATRA and 5% for CTX/ATO/ATRA. Three patients relapsed, two developed therapy-related acute myeloid leukemia and 13 died in remission including seven patients with recurrence of the prior malignancy. Median follow-up for survival was 3.7 years. None of the patients treated with ATRA alone survived beyond one year. Event-free survival was significantly higher after ATO-based therapy (95%, 95% CI, 82–99%) as compared to CTX/ATRA (78%, 95% CI, 64–87%; P=0.042), if deaths due to recurrence of the prior malignancy were censored. The estimated 2-year overall survival in intensively treated patients was 88% (95% CI, 80–93%) without difference according to treatment (P=0.47). ATO when added to ATRA or CTX/ATRA is feasible and leads to better outcomes as compared to CTX/ATRA in t-APL.

Does mean platelet volume really increase in sudden sensorial hearing loss

Dear Editor, Ulu et al. [1] recently published an interesting paper in this journal on the subject of mean platelet volume in patients with sudden idiopathic sensorial hearing loss (SISHL). The authors found a significant increase in the volume of circulating platelets in 40 patients treated in the past 6 years when compared to a group of 40 healthy individuals of identical age and gender. It has been proposed that increased mean platelet volume (and increased platelet activity) may be linked with sudden idiopathic sensorineural hearing loss and that it may indicate ischemia or atherosclerosis as possible causes of SISHL. The publication of Ulu et al. [1] raised considerable interest among readers: editors repeatedly received Letters to the Editor with consensual as well as contradictory opinions, and Ulu et al. published additional interesting ideas in their responses to these Letters to the Editor. Pirodda et al. [2] sent a Letter to the Editor of the European Archives of Oto-Rhino-Laryngology with interesting thoughts on serious functional disorders that can also, in addition to organic disorders, lead to SISHL. It is necessary to respect the relationships between circulation and homeostasis in the inner ear and respect its anatomical structures, the terminal vasculature of the inner ear, and the high-energy demands of this sensory organ. The vascular risk-free population has been extensively studied over the past years and the possibility of cochlear damage associated with SISHL in young and healthy subjects with low blood pressure values was demonstrated. In such cases, abrupt lowering of blood pressure followed by abnormal vasoconstriction could be responsible for the damage [3, 4]. It outlines a link between transiently insufficient peripheral perfusion of systemic origin and acute inner ear sufferance—both detected, for example, in subjects submitted to aggressive anti-hypertensive therapy [5]. Balta et al. [6] sent another Letter to the Editor and pointed to a clinically significant—the question of practical clinical use of mean platelet volume is not simple and comprehensive; the full extent of any assessment must be carried out in relation to a number of other factors. It is of course advantageous that mean platelet volume testing is available during common complete blood count examinations. It is a routine, simple and inexpensive technique that gives a lot of information about the patient’s formed blood contents: the red and white cells, platelets, the counts and dimensions of subgroups of cells as well as parameters, including distribution widths, mean platelet volume, etc. That is why MPV is one of the most widely used laboratory markers related to platelet function based on the inflammatory conditions. As Balta et al. [6] reported, it is advantageous that mean platelet volume is such a simple and accessible marker in addition to being of key importance in the pathophysiology of a number of complex and serious conditions, such as coronary heart disease, endothelial dysfunction and others. Platelet parameters can be affected by coronary risk factors, including age, obesity, This comment refers to the article available at doi:10.1007/s00405013-2348-9.

Prevention of Infection Transmission during Stem Cell Transplantation

Group of 152 patients (investigated before autologous transplantation) and 35 healthy donors for allogeneic transplantation was examined for the risk of infection transmission that can be associated with the infusion of cryopreserved peripheral blood progenitor cells to the patient and/or cross-contamination of stored grafts. No laboratory signs of active infection were found in 22 donors (63 %) and in 91 patients (60%). The most common was active infection by herpes viruses — 50 cases in patients, 21 cases in donors; hepatitis B was found in only two cases. The rate of clinically unsuspected (but dangerous) infections in donors and patients thus remains relatively high in spite of the fact that the system of donor search and the whole transplantation procedure have improved in the last years. The system of safety assurance is extremely important and the whole palette of preventive tests according to EBMT (European Blood and Marrow Transplantation Group) and ISHAGE (International Society for Hemotherapy and Graft Engineering) is fully justified.

Multicentered patient-based evidence of the role of free light chain ratio normalization in multiple myeloma disease relapse

The normalization of free light chain ratio (FLCr) has been introduced as a marker of stringent complete remission (CR) of multiple myeloma (MM). There is currently a lack of literature assessing the role of FLCr on MM disease progression and remission status.

Five years of experience with rituximab plus high-dose dexamethasone for relapsed/refractory chronic lymphocytic leukemia

Introduction High-dose methylprednisolone (HDMP) in combination with rituximab is active in the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL), but serious infections are frequent. Recently published data suggested that high-dose dexamethasone might be equally effective as HDMP despite a lower cumulative dose. Material and methods We performed retrospective analysis of 60 patients with relapsed/refractory CLL (median age: 66 years; range: 37–86) treated with rituximab plus dexamethasone (R-dex) at a single tertiary center between September 2008 and October 2012. The schedule of R-dex consisted of rituximab 500 mg/m2 i.v. day 1 (375 mg/m2 in cycle 1) and dexamethasone 40 mg orally on days 1-4 and 10-13 repeated every 3 weeks for a maximum of 8 cycles. Unfavorable prognostic features were frequent (Rai stages III/IV in 67%, unmutated IgVH 82%, del 11q 43%, TP53 mutation/deletion 23%, bulky lymphadenopathy 58% of patients). Results Overall response (OR)/complete remission (CR) was achieved in 75/3%. At the median follow-up of 21 months, median progression-free survival (PFS) was 8 months, median time to next treatment 12.9 months and median overall survival 25.5 months. Refractoriness to fludarabine (p = 0.04) and age ≥ 65 years (p = 0.03) were significant predictors of shorter PFS. R-dex was successfully used for debulking before allogenic stem cell transplantation in 7 patients (12%). Serious (CTCAE grade III/IV) infections occurred in 27% of patients; 20% of patients developed steroid diabetes requiring temporary short-acting insulin. Conclusions Our results show that R-dex is an active and well-tolerated regimen for patients with relapsed/refractory CLL; however, major infections remain frequent despite combined antimicrobial prophylaxis.

Analysis of Real-world Data on Postremission Therapy for Acute Myeloid Leukemia With Intermediate Risk Cytogenetics in First Complete Remission

Background We retrospectively analyzed data from 310 patients with acute myeloid leukemia with intermediate‐risk cytogenetics in first complete remission (CR1) to evaluate the usage and efficacy of various types of postremission therapy. Patients and Methods Cox regression with time‐dependent covariates, landmark analysis, and competing risk models were used to estimate the outcomes and effects of treatment and patient‐ and disease‐related risk factors. Results The early relapse rate and early nonrelapse mortality (NRM) were 12.8% and 4.4%, respectively. In our study, 77.2% of patients completed postremission therapy: 44% received allogeneic hematopoietic cell transplantation (HCT), 20% completed treatment with high‐dose cytarabine (HIDAC), and 13% completed treatment with intermediate‐dose cytarabine. The 3‐year overall survival rate was 67.5% for patients treated with HIDAC and 63.4% after HCT (P = .5876). The NRM and relapse rate at 3 years were 0% and 58.9% after HIDAC and 21.9% and 29.3% after HCT, respectively. HCT reduced the risk of relapse (hazard ratio, 0.6; 95% confidence interval, 0.36‐0.98). Total body irradiation‐based myeloablative conditioning increased NRM compared with busulfan‐based conditioning (hazard ratio, 8.33; 95% confidence interval, 2.52‐27.45). Conclusion Most patients with acute myeloid leukemia with intermediate‐risk cytogenetics received allogeneic HCT, which decreased the risk of relapse but increased NRM, leading to a similar overall survival for patients who received HCT and HIDAC. Our data support the use of allogeneic transplantation for patients in CR1 from a human leukocyte antigen‐matched related or unrelated donor after a busulfan‐based myeloablative conditioning regimen as a primary strategy of postremission therapy for eligible younger patients. Micro‐Abstract Curative treatment of acute myeloid leukemia (AML) is based on one or two cycles of remission induction chemotherapy followed by consolidation chemotherapy or allogeneic hematopoietic cell transplantation (HCT) in those patients who enter complete remission (CR). We present analysis of course and outcome of post‐remission therapy in 310 patients with AML with intermediate risk cytogenetics.

Is radioiodine administration in patients with papillary thyroid multifocal microcarcinoma unnecessary

Summary Radioiodine (RAI) has played a crucial role in differentiated thyroid cancer treatment for more than 60years. However, the use of RAI administration in patients with papillary thyroid microcarcinoma (even multifocal) is now being widely discussed and often not recommended. In accordance with European consensus, and contrary to the American Thyroid Association (ATA) guidelines, we recently performed RAI thyroid remnant ablation in a patient with differentiated papillary multifocal microcarcinoma. The post-therapeutic whole-body scan and SPECT/CT revealed the real and unexpected extent of disease, with metastases to upper mediastinal lymph nodes. This finding led to the patient’s upstaging from stage I to stage IVa according to the American Joint Committee on Cancer/International Union Against Cancer criteria. Learning points 131I is a combined beta–gamma emitter, thus allowing not only residual thyroid tissue ablation but also metastatic tissue imaging. RAI remnant ablation omission also means post-treatment whole-body scan omission, which may lead to disease underestimation, due to incorrect nodal and metastatic staging. RAI should be considered also in “low-risk” patients, especially when the lymph node involvement is not reliably documented. Lower administered RAI activity (30mCi, 1.1GBq) may be a workable compromise in low-risk patients, not indicated for RAI remnant ablation according to ATA guidelines.

Ten years’ experience with four cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, procarbazine (BEACOPP)-escalated followed by four cycles of baseline-dose BEACOPP in patients with advanced stage Hodgkin lymphoma: a single-center, retrospective study

Abstract The HD-9 trial showed that eight cycles of BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, procarbazine)-escalated led to significant improvements in response rate, progression-free survival and overall survival over COPP/ABVD (cyclophosphamide, vincristine, prednisone, procarbazine/doxorubicin, bleomycin, vinblastine, dacarbazine) therapy. This monocentric retrospective study was performed to evaluate 10 years of experience with four cycles of BEACOPP-escalated and four cycles of BEACOPP-baseline outside of clinical trials. The outcomes were assessed in 78 patients with newly diagnosed advanced stage Hodgkin lymphoma. A complete response after chemotherapy ± radiotherapy was achieved in 75 patients (96%). At the median follow-up of 74 months, the actuarial 5- and 10-year freedom from treatment failure (FFTF) rates were 91% and 89%, and actuarial 5- and 10-year overall survival rates for the entire group were 93% and 90%, respectively. These results suggest that the combination of escalated and baseline BEACOPP chemotherapy is feasible in routine practice with good efficacy and acceptable toxicity.