Head-to-head comparison of [68Ga]Ga-PSMA-11 and [18F]FDG PET/CT in multiple myeloma.

PURPOSE: The aim of this study was to compare [18F]FDG and [68Ga]Ga-PSMA-11 PET/CT image findings in patients with multiple myeloma (MM). METHODS: Twenty consecutive patients with symptomatic biopsy-proven MM were submitted to whole body [18F]FDG and [68Ga]Ga-PSMA-11 PET/CT with a time interval of 1-8 days between procedures. All lesions were counted and had their maximum SUV (SUVmax) measured. Intra-class correlation (ICC) was used to assess the agreement between [18F]FDG and [68Ga]Ga-PSMA-11 PET/CT findings. RESULTS: A total of 266 lesions were detected in 19/20 patients. [18F]FDG detected 223/266 (84%) lesions in 17 patients and [68Ga]Ga-PSMA-11 190/266 (71%) lesions in 19 patients. Both procedures did not identify any active lesion in 1 patient. Forty-three (16%) lesions were detected only by [68Ga]Ga-PSMA-11 and 76 (29%) only by [18F]FDG. Both tracers identified 147 (55%) lesions. Intralesional mismatch of FDG-PSMA uptake was identified in 25 of these 147 lesions, found in 8 different patients. Different lesions with uptake of only [18F]FDG or [68Ga]Ga-PSMA-11 in the same patient were found in 4 patients. The highest SUVmax of [18F]FDG and [68Ga]Ga-PSMA-11 had a median (min-max) SUVmax of 6.5 (2.0-37.8) and 5.5 (1.7-51.3), respectively. [18F]FDG and [68Ga]Ga-PSMA-11 respectively identified 18 and 19 soft tissue lesions. False-positive [18F]FDG findings had minimal or no uptake of [68Ga]Ga-PSMA-11. Good reliability (ICC ≥ 0.75) was found for number of lesions, number of soft tissue lesions and highest SUVmax in each patient. CONCLUSION: [18F]FDG or [68Ga]Ga-PSMA-11 alone can detect most MM lesions. Almost half of the lesions take up only one of the tracers, reflecting increased glycolysis or angiogenesis in specific lesions, and suggesting their possible complementary role in MM. The marked [68Ga]Ga-PSMA-11 uptake in some cases raises the possibility of a theranostic approach in selected patients.

Effects of a physiotherapeutic protocol in cardiorespiratory, muscle strength, aerobic capacity and quality of life after hematopoietic stem cell transplantation.

OBJECTIVE: To analyze the effects of hospital cardiorespiratory physical therapy protocol on the functional capacity and quality of life of patients submitted to hematopoietic stem cell transplantation (HSCT). METHODS: From January to December 2019, bilateral dynamometry, Manovacuometry and Ventilometry, peak expiratory flow "Peak Flow", 6-min walk test (6MWT), SF-36 Quality of Life Questionnaire and Visual Analog Scale (VAS) were applied in patients who have undergone an allogeneic or autologous hematopoietic stem cell transplantation (HSCT), pre-conditioning (initial evaluation) and pre-discharge (final evaluation). The patients were submitted to an intervention protocol, consisting of aerobic training, muscle strengthening and respiratory muscle training, between the two assessments. RESULTS: 29 patients were enrolled in the study and 24 (83%) completed all procedure. Myeloablative and reduced intensity conditioning were performed in 89.6% and 10.4%, respectively; 17 (58%) patients have undergone an autologous HSCT; 10 (35%) identical related allogeneic HSCT, and 2 (7%) haploidentical allogeneic HSCT. The median number of interventions per patient was 3 (1-9). A decreasing in the right and left dynamometry (p  ≤ 0.0001 and 0.002, respectively) and, also in the distance covered in the 6MWT (p  = 0.004), was observed after HSCT. There was no significant difference in respiratory muscle strength, quality of life and fatigue sensation. CONCLUSION: Cardiorespiratory rehabilitation can preserve functional capacity and quality of life.

Effects of a physiotherapeutic protocol in cardiorespiratory, muscle strength, aerobic capacity and quality of life after hematopoietic stem cell transplantation

Abstract Objective To analyze the effects of hospital cardiorespiratory physical therapy protocol on the functional capacity and quality of life of patients submitted to hematopoietic stem cell transplantation (HSCT). Methods From January to December 2019, bilateral dynamometry, Manovacuometry and Ventilometry, peak expiratory flow "Peak Flow", 6-min walk test (6MWT), SF-36 Quality of Life Questionnaire and Visual Analog Scale (VAS) were applied in patients who have undergone an allogeneic or autologous hematopoietic stem cell transplantation (HSCT), pre-conditioning (initial evaluation) and pre-discharge (final evaluation). The patients were submitted to an intervention protocol, consisting of aerobic training, muscle strengthening and respiratory muscle training, between the two assessments. Results 29 patients were enrolled in the study and 24 (83%) completed all procedure. Myeloablative and reduced intensity conditioning were performed in 89.6% and 10.4%, respectively; 17 (58%) patients have undergone an autologous HSCT; 10 (35%) identical related allogeneic HSCT, and 2 (7%) haploidentical allogeneic HSCT. The median number of interventions per patient was 3 (1-9). A decreasing in the right and left dynamometry (p ≤ 0.0001 and 0.002, respectively) and, also in the distance covered in the 6MWT (p = 0.004), was observed after HSCT. There was no significant difference in respiratory muscle strength, quality of life and fatigue sensation. Conclusion Cardiorespiratory rehabilitation can preserve functional capacity and quality of life.

Characteristics and clinical outcomes of patients with ALK-positive anaplastic large cell lymphoma: Report from the prospective international T-cell lymphoma project.

The T-cell Lymphoma Project is an international registry prospective study that enrolled patients with newly diagnosed peripheral T-cell and NK-cell lymphomas (PTCL). The main objective was to define the clinical features and outcomes, establishing a robust benchmark for future clinical trials. Seventy-four institutions from 14 countries in North America, South America, Europe, and Asia collected data on patients diagnosed and treated at their respective centers between September 2006 and February 2018. Among 1553 PTCL patients, 131 (8.4% of the total cohort) were confirmed to have anaplastic large cell lymphoma - kinase positive (ALCL, ALK+). The median age of the patients was 39 years (18-84). Sixty-five patients (66%) had advanced-stage disease, although majority (45 patients, 54%) had a low-risk International Prognostic Index (IPI) score (0-1). Of 97 patients treated with chemotherapy, 97% received anthracycline-containing regimens. The overall response rate was 81%, with 69 patients (70%) achieving complete remission. Estimated OS and PFS at 3 years were 77% (95% CI: 54%-99%) and 68% (95% CI: 46%-90%), respectively, and at 5 years were very similar, 77% of OS (95% CI: 62%-92%) and 64% of PFS (95% CI: 34%-94%). Multivariate analysis for PFS showed advanced stage (hazard ratios [HR]: 4.72, 95% CI: 1.43-23.9, p = 0.015), elevated lactate dehidrogenade (LDH) (HR 4.85; 95% CI: 1.73-13.60, p = 0.001), and Eastern Cooperative Oncology Group Performance Status scale (ECOG-PS) ≥2 (HR: 5.25; 95% CI: 1.68-16.4, p = 0.024). For OS, elevated LDH (HR: 3.77; 95% CI: 1.98-14.17, p = 0.014) and ECOG-PS ≥2 (HR: 4.59; 95% CI: 1.46-14.39, p = 0.004) were identified. In summary, although the outcome of ALK+ ALCL is superior to that of other PTCLs, it remains sufficiently favorable, given the young median age of the patients. Our results confirm the usefulness of both IPI and Prognostic Index for T-cell Lymphoma (PIT) in identifying groups of patients with different outcomes. Clinical Trials ID: NCT01142674.

Head-to-head comparison between 68Ga-PSMA and 18F-FDG-PET/CT in lymphomas: a preliminary analysis.

PURPOSE: Isolated case reports mention the uptake of radiolabeled PSMA in lymphoma. However, it is not clear if the intensity of 68Ga-PSMA expression varies among different histological subtypes or if it correlates with 18F-FDG uptake. This study compared both tracers in patients with diverse lymphoma subtypes. METHODS: Ten patients with biopsy-proven-lymphoma underwent 18F-FDG and 68Ga-PSMA-PET/CT (maximum time interval: 6 days). Lymphoma subtypes included Hodgkin's lymphoma (HL, three patients) and aggressive and indolent non-Hodgkin's lymphoma (NHL, seven patients). The intensity of PSMA uptake was classified visually as low, intermediate, or high, using blood pool, liver and parotid gland uptake as references. Maximum standardized-uptake value (SUVmax) of each affected site was measured in both sets of images. RESULTS: FDG detected 59/59 involved sites in 10 patients and PSMA 47/59 sites in nine patients. PSMA uptake was generally low, regardless of the intensity of FDG uptake, but it was classified as intermediate in two patients. The median SUVmax varied from 2.0 (2.0-8.2) to 30.9 for FDG and from 1.7 (1.7-1.7) to 4.4 for PSMA, P < 0.0001. The primary lesion of one patient had a marked intralesional mismatch uptake pattern of the tracers, with areas of higher PSMA expression than FDG uptake, and vice-versa. A brain lesion was more easily identified with PSMA than with FDG images. CONCLUSION: HL and several NHL subtypes may present PSMA uptake. The intensity of PSMA expression is generally lower than that of FDG uptake and seems to present less variation among the different histological subtypes of lymphomas.

99mTc-sestamibi SPECT/CT and 18F-FDG-PET/CT have similar performance but different imaging patterns in newly diagnosed multiple myeloma.

PURPOSE: F-fluorodeoxiglucose (F-FDG)-PET/CT has been widely used to evaluate multiple myeloma. Tc-sestamibi (MIBI) scintigraphy has also been proposed for assessing multiple myeloma, but its use with state-of-the-art single-photon emission computed tomography/computed tomography (SPECT/CT) technology has not been fully evaluated.This study aimed to compare these two imaging modalities in multiple myeloma staging. MATERIALS AND METHODS: Sixty-two patients with recently diagnosed multiple myeloma were submitted to whole-body F-FDG-PET/CT and whole-body MIBI scans plus SPECT/CT of the chest and abdomen/pelvis. Number of focal lesions, contiguous soft tissue involvement (CSTI), extramedullary lesions (EMLs) and diffuse bone marrow (BM) involvement were recorded. RESULTS: PET/CT was positive in 59 patients (95%) and MIBI SPECT/CT in 58 (93%) (P = 0.69). MIBI detected more diffuse bone marrow involvement than PET/CT (respectively 78 vs. 58% of the patients), while PET/CT demonstrated more focal lesions than MIBI SPECT/CT (81 vs. 54% of the patients) (P = 0.002). PET/CT detected EMLs in four subjects and MIBI in one subject. CSTI was found in 28 (45%) and 23 (37%) patients on PET/CT and MIBI images, respectively (P = 0.36). Three patients with lytic lesions and no FDG uptake were MIBI positive, and two subjects with lytic lesions without MIBI uptake were FDG positive. CONCLUSION: MIBI SPECT/CT performs similarly to F-FDG-PET/CT in identifying sites of active disease in multiple myeloma staging. MIBI is more efficient than FDG for detecting the diffuse involvement of bone marrow but less efficient for detecting focal lesions. Some patients presented a 'mismatch' pattern of FDG/MIBI uptake.

Survival outcomes of patients with extranodal natural-killer T-cell lymphoma: a prospective cohort study from the international T-cell Project.

BACKGROUND: Extranodal natural killer (NK) T-cell lymphoma (ENKTL) is a unique clinicopathological entity, typically associated with poor survival outcomes. Most published data have come from east Asian study groups, with little information available from international cohorts. The effects of treatment advances on routine clinical practice across continental territories has not been clear. We aimed to improve understanding of the clinical characteristics and outcomes of patients with ENKTL. METHODS: We did a substudy of patients with ENKTL from the T-cell Project, a global prospective cohort study. The T-cell Project registered consecutively diagnosed adults (>18 years) with newly diagnosed, untreated mature T-cell or NK lymphomas (WHO 2001 or 2008 classifications) from 74 centres in 13 countries (in Asia, Europe, North America, and South America). In total, 1695 patients with mature T-cell or NK lymphomas were enrolled between Oct 12, 2006 and Feb 28, 2018 in the T-cell Project. The first patient with ENKTL was enrolled on Feb 15, 2007, and the last on May 26, 2017. Data on baseline characteristics, first-line treatment, treatment response, and survival outcomes were recorded in a central database (locked March 30, 2019). The primary outcome was 5-year overall survival. The T-cell Project is registered on ClinicalTrials.gov, NCT01142674. FINDINGS: 166 patients were diagnosed with ENKTL, comprising 11% of 1553 eligible registered cases and distributed across 40 participating centres in four continents. At a median follow-up of 44 months (IQR 20-61), overall survival at 5 years was 54% (95% CI 44-63) in patients with nasal disease (n=98) and 34% (27-46) in patients with extranasal disease (n=68). INTERPRETATION: To our knowledge, this study presents the largest international cohort of patients with ENKTL. We describe a clinically significant improvement in the survival of patients with ENKTL treated in routine clinical practice over the past decade, likely to be attributable to the increasing use of treatment protocols specific for ENKTL. FUNDING: The Fondazione Cassa di Risparmio di Modena, the Associazione Angela Serra per la Ricerca sul Cancro, the Fondazione Italiana Linfomi, Allos Therapeutics, Spectrum Pharmaceuticals, Associazione Italiana per la Ricerca sul Cancro, and the National Cancer Institute at the National Institutes of Health.

Validation of a Multifocal Segmentation Method for Measuring Metabolic Tumor Volume in Hodgkin Lymphoma.

Quantification of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) can be time-consuming. We evaluated the performance of an automatic multifocal segmentation (MFS) method of quantification in patients with different stages of Hodgkin lymphoma, using the multiple VOI (MV) method as reference. Methods: This prospective bicentric study included 50 patients with Hodgkin lymphoma who underwent staging 18F-FGD PET/CT. The examinations were centrally reviewed and processed with commercial MFS software to obtain MTV and TLG using 2 fixed relative thresholds (40% and 20% of SUVmax) for each lesion. All PET/CT scans were processed using the MV and MFS methods. Interclass correlation coefficients and Bland-Altman plots were used for statistical analysis. Repeated calculations of MTV and TLG values by 2 observers with different degrees of PET/CT imaging experience were used to ascertain interobserver agreement on the MFS method. Results: The means and SDs obtained for the MTV with MV and MFS were, respectively, 736 ± 856 mL and 660 ± 699 mL for the 20% threshold and 313 ± 359 mL and 372 ± 434 mL for the 40% threshold. The time spent calculating the MTV was much shorter with the MFS method than with the MV method (median time, 11.6 min [range, 1-30 min] and 64.4 min [range, 1-240 min], respectively), especially in patients with advanced disease. Time spent was similar in patients with localized disease. There were no statistical differences between the MFS values obtained by the 2 different observers. Conclusion: MTV and TLG calculations using MFS are reproducible, generate similar results to those obtained with MV, and are much less timing-consuming. Main differences between the 2 methods were related to difficulties in avoiding overlay of VOIs in the MV technique. MV and MFS perform equally well in patients with a small number of lesions.

Treatment with dasatinib or nilotinib in chronic myeloid leukemia patients who failed to respond to two previously administered tyrosine kinase inhibitors--a single center experience.

OBJECTIVE: To evaluate hematological, cytogenetic and molecular responses as well as the overall, progression-free and event-free survivals of chronic myeloid leukemia patients treated with a third tyrosine kinase inhibitor after failing to respond to imatinib and nilotinib/dasatinib. METHODS: Bone marrow karyotyping and real-time quantitative polymerase chain reaction were performed at baseline and at 3, 6, 12 and 18 months after the initiation of treatment with a third tyrosine kinase inhibitor. Hematologic, cytogenetic and molecular responses were defined according to the European LeukemiaNet recommendations. BCR-ABL1 mutations were analyzed by Sanger sequencing. RESULTS: We evaluated 25 chronic myeloid leukemia patients who had been previously treated with imatinib and a second tyrosine kinase inhibitor. Nine patients were switched to dasatinib, and 16 patients were switched to nilotinib as a third-line therapy. Of the chronic phase patients (n=18), 89% achieved a complete hematologic response, 13% achieved a complete cytogenetic response and 24% achieved a major molecular response. The following BCR-ABL1 mutations were detected in 6/14 (43%) chronic phase patients: E255V, Y253H, M244V, F317L (2) and F359V. M351T mutation was found in one patient in the accelerated phase of the disease. The five-year overall, progression-free and event-free survivals were 86, 54 and 22% (p<0.0001), respectively, for chronic phase patients and 66%, 66% and 0% (p<0.0001), respectively, for accelerated phase patients. All blast crisis patients died within 6 months of treatment. Fifty-six percent of the chronic phase patients lost their hematologic response within a median of 23 months. CONCLUSIONS: Although the responses achieved by the third tyrosine kinase inhibitor were not sustainable, a third tyrosine kinase inhibitor may be an option for improving patient status until a donor becomes available for transplant. Because the long-term outcome for these patients is poor, the development of new therapies for resistant chronic myeloid leukemia patients is necessary.

Treatment with dasatinib or nilotinib in chronic myeloid leukemia patients who failed to respond to two previously administered tyrosine kinase inhibitors - a single center experience

OBJECTIVE: To evaluate hematological, cytogenetic and molecular responses as well as the overall, progression-free and event-free survivals of chronic myeloid leukemia patients treated with a third tyrosine kinase inhibitor after failing to respond to imatinib and nilotinib/dasatinib. METHODS: Bone marrow karyotyping and real-time quantitative polymerase chain reaction were performed at baseline and at 3, 6, 12 and 18 months after the initiation of treatment with a third tyrosine kinase inhibitor. Hematologic, cytogenetic and molecular responses were defined according to the European LeukemiaNet recommendations. BCR-ABL1 mutations were analyzed by Sanger sequencing. RESULTS: We evaluated 25 chronic myeloid leukemia patients who had been previously treated with imatinib and a second tyrosine kinase inhibitor. Nine patients were switched to dasatinib, and 16 patients were switched to nilotinib as a third-line therapy. Of the chronic phase patients (n=18), 89% achieved a complete hematologic response, 13% achieved a complete cytogenetic response and 24% achieved a major molecular response. The following BCR-ABL1 mutations were detected in 6/14 (43%) chronic phase patients: E255V, Y253H, M244V, F317L (2) and F359V. M351T mutation was found in one patient in the accelerated phase of the disease. The five-year overall, progression-free and event-free survivals were 86, 54 and 22% (p<0.0001), respectively, for chronic phase patients and 66%, 66% and 0% (p<0.0001), respectively, for accelerated phase patients. All blast crisis patients died within 6 months of treatment. Fifty-six percent of the chronic phase patients lost their hematologic response within a median of 23 months. CONCLUSIONS: Although the responses achieved by the third tyrosine kinase inhibitor were not sustainable, a third tyrosine kinase inhibitor may be an option for improving patient status until a donor becomes available for transplant. Because the long-term outcome ...

Impairment of thrombin generation in the early phases of the host response of sepsis.

PURPOSE: The purpose was to investigate the presence of hypercoagulability in the very early phase of the host response to an infection in the clinical course of sepsis and septic shock. MATERIAL AND METHODS: Twenty-four patients with chemotherapy-associated febrile neutropenia were evaluated at baseline, at the time of fever onset, and 48 hours thereafter using the thrombin generation test, a more physiological and global assay of hemostasis. RESULTS: The rate of thrombin generation was decreased and no signals of systemic hypercoagulability could be observed during the first 48 hours of sepsis. Moreover, patients that evolved to septic shock presented a more significant impairment in thrombin generation than those with noncomplicated sepsis. CONCLUSIONS: Patients with sepsis and febrile neutropenia present an impairment in thrombin generation from very early stages of their disease course. These results suggest that the procoagulant in vitro alterations described during sepsis do not necessarily translate into a clinically relevant systemic hypercoagulable state. These findings could help explain why treatment with systemic anticoagulants did not translate to clinical benefits in human sepsis and highlight the need for a better understanding of the hemostatic alterations in sepsis before new treatments targeting coagulation activation are developed.

Protein-coding genes and long noncoding RNAs are differentially expressed in dasatinib-treated chronic myeloid leukemia patients with resistance to imatinib.

Dasatinib has demonstrated efficacy in patients with chronic-phase chronic myeloid leukemia (CML) who had resistance or intolerance to imatinib. However, some patients also develop resistance or intolerance to dasatinib. To identify potential molecular pathways involved in primary resistance to dasatinib in CML, we analyzed gene expression profiles of mononuclear cells of 7 imatinib-resistant patients, collected before and after 1-year dasatinib treatment. Large-scale gene expression was measured with Agilent microarrays covering protein-coding genes and long (>200 nt) noncoding RNAs (lncRNAs). Sets of genes and lncRNAs significantly differentially expressed (>1.5 fold-change; q value ≤10%) were identified. Ingenuity Pathway Analysis pointed to a number of functions, canonical pathways and gene networks that were significantly enriched with differentially expressed genes. In addition to protein-coding genes, lncRNAs have been recently implicated in pathways leading to tumorigenesis. Our data point to new possible regulatory elements involved in dasatinib resistance in CML.

Cytomegalovirus (CMV) genotype in allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Based on sequence variation in the UL55 gene that encodes glycoprotein B (gB), human cytomegalovirus (CMV) can be classified into four gB genotypes. Previous studies have suggested an association between CMV gB genotype and clinical outcome in patients who underwent an allogeneic hematopoietic stem cell transplant (HSCT). The goals of this study were identify patients with active infection caused by CMV in recipients of HSCT; determine the prevalence of CMV genotypes in the study group; correlate genotype with CMV disease, acute GVHD and overall survival. METHODS: The diagnosis of active CMV infection after allogeneic HSCT was detected by antigenemia (AGM) and/or nested-PCR (N-PCR). Positive samples from patients with active CMV infection were submitted to genotyping using N-PCR to amplify a region of UL55, followed by restriction analysis based on HinfI and RsaI digestion. Real-time PCR (qPCR) was used to determine the viral load during active CMV infection and antiviral treatment. RESULTS: Sixty-three allogeneic HSCT recipients were prospectively evaluated; 49/63 (78%) patients were infected with CMV genotypes - gB1 19/49 (39%), gB2 17/49 (35%), gB3 3/49 (6%), gB4 7/49 (14%) - and 3 (6%) had mixed CMV genotypes (gB1 + gB3, gB1 + gB4 and gB2 + gB4). Characterized by gastrointestinal disease, CMV disease occurred in 3/49 (6.1%) patients, who had CMV gB3 genotype. These gB3 genotype patients presented an increasing AGM number, mean 125 (± 250) (P = 0.70), and qPCR copies/ml, mean 37938 (SD ± 50542) (P = 0.03), during antiviral treatment, when compared with other CMV genotypes. According to CMV genotypes, stratified overall survival was 55% for gB1, 43% for gB2; 0% for gB3 and 57% for gB4 (P = 0.03). CONCLUSIONS: One of the restrictions of the presented study was the low number of CMV gB sub-cohorts). However, we demonstrated that the frequency of active CMV infection in this HSCT population was high, and the most prevalent genotype in these patients with active CMV infection was gB1 and gB2 genotype (74%). In Brazil, HSCT recipients seem to carry mainly gB1 and gB2 CMV genotype.

Quantifying loss of CD34+ cells collected by apheresis after processing for freezing and post-thaw.

INTRODUCTION: CD34(+) cells collected for autologous bone marrow transplantation (BMT) are usually quantified in the apheresis product after collection, but the necessity to repeat these measures post-thaw is controversial. METHODS: We examined the loss of CD34(+) cells after collection, preparation for freezing and post-thaw in apheresis products collected for BMT. RESULTS: Median number of CD34(+) cells collected per unit was 1.61×10(6)/kg, viability: 97-100%. This number decreased to 1.38×10(6)/kg, viability: 96-100% before freezing and was 1.17×10(6)/kg post-thaw. Viability decreased to 86-98%. The relative loss of viable PBHPC showed an inverse correlation with the ratio "CD34(+) cells/total nucleated cells" (r=-0.45; p=<0.0005). This relative loss was largest in patients with Hodgkin's lymphoma. CONCLUSION: Cryopreservation and thawing of PBHPCs in leukapheresis products provokes a small but significant stem cell loss. So, quantification of viable CD34(+) cells post-thaw is important, especially in poorly mobilizing patients. Besides, the ratio "CD34(+) cells/total nucleated cells" after leukapheresis is an important parameter for prediction of neutrophil recovery after BMT.

Adherence to tyrosine kinase inhibitor therapy for chronic myeloid leukemia: a Brazilian single-center cohort.

The introduction of oral tyrosine kinase inhibitors (TKIs) has dramatically improved outcomes in chronic myeloid leukemia (CML) patients. However, treatment success is directly related to good long-term adherence. Adherence to TKI therapy was evaluated in 137 CML patients over a period of 1 year. Three different methods were used to evaluate adherence: the Morisky questionnaire, a medication diary and the medication possession ratio (MPR). MPR was the most effective method of assessing adherence (median adherence 96.5%; p = 0.0001), duration of TKI treatment was the variable that most impacted adherence (p = 0.03), and the MPR was inversely correlated to the duration of therapy. Additionally, participation in clinical trials, better quality of life as reported by patients and higher socioeconomic status were all related to better compliance (p = 0.02, 0.007 and 0.01, respectively). For patients treated with imatinib for 24-48 months (n = 22), individuals with major molecular response (MMR) had a significantly better MPR than those who failed to achieve MMR (p = 0.04). In this group, the mean MPR was 87% for the population without apparent molecular response and 96% for those achieving MMR; however, only 24% of the patients were completely adherent to TKI treatment.

Risk factors for impaired gonadal function in female Hodgkin lymphoma survivors: final analysis of a retrospective multicenter joint study from Italian and Brazilian Institutions.

Hodgkin lymphoma (HL) is one of the most common types of cancer in the young and one of the most curable forms of cancer. Therefore, there has been an increasing interest in the study of long-term morbidities. The aims of the present study were to evaluate the prevalence and risk factors for impaired gonadal function in a retrospective cohort of 238 HL female survivors from Italy and Brazil and to analyse the role of oral contraceptives (OC) and GnRH-analogues. Besides data collection from HL databases, a specific questionnaire was administered to collect data on gonadal function. The median age at diagnosis was 25 years and the median follow-up was 7 years. Overall, 25% of the patients developed impaired gonadal function. Older age at diagnosis, front-line therapies containing alkylating agents and more than one treatment were independent risk factors, whereas the use of OC or GnRH-a reduced independently the risk of impaired gonadal function. The fertility rate among fertile survivors was low when compared with the general population. We confirmed that older age, type of front-line chemotherapy and a higher number of therapies are associated with gonadal function impairment in terms of infertility and premature menopause in female HL survivors. Also, the use of GnRH-a or OC was independently identified as a protective factor. Further prospective studies are needed to better understand the barriers to parenthood in HL survivors.