STUDY QUESTION: What is the impact of the EuroNet-PHL-C2 treatment for boys with classical Hodgkin lymphoma (cHL) on semen parameters? SUMMARY ANSWER: More than half of the patients (52%, n = 16/31) had oligozoospermia or azoospermia at 2 years from cHL diagnosis; particularly boys treated for advanced-stage cHL had low sperm counts and motility. WHAT IS KNOWN ALREADY: Chemotherapy and radiotherapy to the inguinal region or testes can impair spermatogenesis and result in reduced fertility. The EuroNet-PHL-C2 trial aims to minimize radiotherapy in standard childhood cHL treatment, by intensifying chemotherapy. The present study aims to assess the (gonadotoxic) impact of this treatment protocol on semen parameters and reproductive hormones in boys aged ≤18 years. STUDY DESIGN, SIZE, DURATION: This international, prospective, multi-centre cohort study was an add-on study to the randomized phase-3 EuroNet-PHL-C2 trial, where the efficacy of standard cHL treatment with OEPA-COPDAC-28 (OEPA: vincristine, etoposide, prednisone, and doxorubicin; COPDAC-28: cyclophosphamide, vincristine, prednisone, and dacarbazine) was compared to intensified OEPA-DECOPDAC-21 chemotherapy (DECOPDAC-21: COPDAC with additional doxorubicin and etoposide and 25% more cyclophosphamide). Patients were recruited between January 2017 and September 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: Eligibility criteria included male patients, diagnosed with classical HL before or at the age of 18 years, and treated according to the EuroNet-PHL-C2 protocol in any of the 18 participating sites in the Netherlands, Germany, Belgium, Czech Republic, and Austria. Sperm parameters (sperm concentration, progressive motility, sperm volume, and calculated total motile sperm count) were assessed at diagnosis and 2 years after diagnosis in (post)pubertal boys. Laboratory measurements (serum follicle-stimulating hormone (FSH) and inhibin B) were performed in samples drawn at diagnosis, during treatment (2-3 times), and at 2 years post-diagnosis, and (age-adjusted) analyses were conducted separately for pre-pubertal and (post)pubertal boys. Outcomes were compared between the treatment levels (TL1, TL2, and TL3) and consolidation treatment schemes (COPDAC-28 and DECOPDAC-21). MAIN RESULTS AND THE ROLE OF CHANCE: In total, 101 boys were included in the present analysis: 73 were (post)pubertal (median age 15.4 years, (IQR 14.4; 16.6), 10 TL1, 29 TL2, 34 TL3, 62% of TL2/3 patients received COPDAC-28) and 28 boys were pre-pubertal (median age 9.6 years (IQR 6.6; 11.4), 4 TL1, 7 TL2, 17 TL3, 38% of TL2/3 patients received COPDAC-28). The study included six boys who had received pelvic radiotherapy; none were irradiated in the inguinal or testicular area. At diagnosis, 48 (post)pubertal boys delivered semen for cryopreservation; 19 (40%) semen samples were oligospermic and 4 (8%) were azoospermic. Low sperm concentration (<15 mil/ml) appeared to be related to the HL disease itself, with a higher prevalence in boys who presented with B symptoms (76% vs 26%, aOR 2.3 (95% CI 1.0; 3.8), P = 0.001) compared to those without such symptoms. At 2 -years post-diagnosis, 31 boys provided semen samples for analysis, of whom 12 (39%) boys had oligozoospermia and 4 (13%) had azoospermia, while 22 boys (71%) had low total motile sperm counts (TMSC) (<20 mil). Specifically, the eight boys in the TL3 group treated with DECOPDAC-21 consolidation had low sperm counts and low progressive motility after 2 years (i.e. median sperm count 1.4 mil/ml (IQR <0.1; 5.3), n = 7 (88%), low sperm concentration, low median progressive motility 16.5% (IQR 0.0; 51.2), respectively). Age-adjusted serum FSH levels were significantly raised and inhibin B levels (and inhibin B:FSH ratios) were decreased during chemotherapy in (post)pubertal boys, with subsequent normalization in 80% (for FSH) and 60% (for inhibin B) of boys after 2 years. Only 4 out of the 14 (post)pubertal boys (29%) with low sperm concentrations after 2 years had elevated FSH (>7.6 IU/l), while 7 (50%) had low inhibin B levels (<100 ng/l). In pre-pubertal boys, reproductive hormones were low overall and remained relatively stable during chemotherapy. LIMITATIONS, REASONS FOR CAUTION: The present analyses included sperm and laboratory measurements up to 2 years post-diagnosis. Long-term reproductive outcomes and potential recovery of spermatogenesis remain unknown, while recovery was reported up to 5- or even 10-year post-chemotherapy in previous studies.Boys who were pre-pubertal at diagnosis were still too young and/or physically not able to deliver semen after 2 years and we could not assess a potential difference in gonadotoxicity according to pubertal state at the time of treatment. Overall, the statistical power of the analyses on sperm concentration and quality after 2 years was limited. WIDER IMPLICATIONS OF THE FINDINGS: Results of the semen analyses conducted among the 31 boys who had provided a semen sample at 2 years post-treatment were generally poor. However, additional long-term and adequately powered data are crucial to assess the potential recovery and clinical impact on fertility. The participating boys will be invited to deliver a semen sample after 5 years. Until these data become available, benefits of intensified chemotherapy in cHL treatment to reduce radiotherapy and lower risk for development of secondary tumours should be carefully weighed against potentially increased risk of other late effects, such as diminished fertility due to the increased chemotherapy burden. Boys with newly diagnosed cHL should be encouraged to deliver sperm for cryopreservation whenever possible. However, patients and clinicians should also realize that the overall state of disease and inflammatory milieu of cHL can negatively affect sperm quality and thereby reduce chance of successful fertility preservation. Furthermore, the measurement of FSH and inhibin B appears to be of low value in predicting low sperm quality at two years from cHL treatment. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Dutch charity foundation KiKa (project 257) that funds research on all forms of childhood cancer. C.M.-K., D.K., W.H.W., D.H., MC, A.U., and A.B. were involved in the development of the EuroNet-PHL-C2 regimen. The other authors declare no potential conflict of interest. TRIAL REGISTRATION NUMBER: N/A.
- MeSH
- analýza spermatu MeSH
- azoospermie farmakoterapie MeSH
- cyklofosfamid * terapeutické užití MeSH
- dakarbazin terapeutické užití MeSH
- dítě MeSH
- doxorubicin terapeutické užití škodlivé účinky MeSH
- etoposid terapeutické užití aplikace a dávkování MeSH
- folikuly stimulující hormon krev MeSH
- Hodgkinova nemoc * farmakoterapie MeSH
- inhibiny krev MeSH
- lidé MeSH
- mladiství MeSH
- motilita spermií účinky léků MeSH
- oligospermie farmakoterapie MeSH
- počet spermií MeSH
- prednison terapeutické užití aplikace a dávkování MeSH
- předškolní dítě MeSH
- prospektivní studie MeSH
- protokoly antitumorózní kombinované chemoterapie * terapeutické užití škodlivé účinky MeSH
- vinkristin terapeutické užití MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
STUDY QUESTION: What is the impact of the EuroNet-PHL-C2 treatment protocol for children with classical Hodgkin lymphoma (cHL) on gonadal function in girls, based on assessment of serum anti-Müllerian hormone (AMH)? SUMMARY ANSWER: Serum AMH levels decreased after induction chemotherapy and increased during subsequent treatment and 2 years of follow-up, with lowest levels in patients treated for advanced stage cHL. WHAT IS KNOWN ALREADY: Treatment for cHL, particularly alkylating agents and pelvic irradiation, can be gonadotoxic and result in premature reduction of primordial follicles in females. The current EuroNet-PHL-C2 trial aims to reduce the use of radiotherapy in standard childhood cHL treatment, by intensifying chemotherapy. This study aims to assess the gonadotoxic effect of the EuroNet-PHL-C2 protocol. STUDY DESIGN, SIZE, DURATION: This international, prospective, multicenter cohort study is embedded in the EuroNet-PHL-C2 trial, an European phase-3 treatment study evaluating the efficacy of standard cHL treatment with OEPA-COPDAC-28 (OEPA: vincristine, etoposide, prednisone, and doxorubicin; COPDAC-28: cyclophosphamide, vincristine, prednisone, and dacarbazine) versus intensified OEPA-DECOPDAC-21 (DECOPDAC-21: COPDAC with additional doxorubicin and etoposide and 25% more cyclophosphamide) in a randomized setting. Participants were recruited between January 2017 and September 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: Female patients aged ≤18 years, treated according to the EuroNet-PHL-C2 protocol for cHL were recruited across 18 sites in the Netherlands, Belgium, Germany, Austria, and Czech Republic. All parents and patients (aged ≥12 years old) provided written informed consent. Serum AMH levels and menstrual cycle characteristics were evaluated over time (at diagnosis, one to three times during treatment and 2 up to 5 years post-diagnosis) and compared between treatment-levels (TL1, TL2, and TL3) and treatment-arms (OEPA-COPDAC-28 and OEPA-DECOPDAC-21). Serum samples obtained from patients after receiving pelvic radiotherapy were excluded from the main analyses. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 104 females, with median age at diagnosis of 15.6 years (IQR 13.7; 17.0), were included in the analysis. Ninety-nine were (post)pubertal. Eighteen girls were diagnosed with an early stage of cHL (TL1) and 86 with intermediate or advanced stage disease (50 TL2 and 36 TL3, 66% received COPDAC-28 and 34% DECOPDAC-21). Five patients received pelvic radiotherapy. Median AMH level at diagnosis was 1.7 μg/l (IQR 0.9; 2.7). After two courses of OEPA chemotherapy, AMH levels decreased substantially in all patients (98% <0.5 μg/l), followed by a significant increase during the consolidation treatment and follow-up. After 2 years, 68% of patients reached their baseline AMH value, with overall median recovery of 129% (IQR 75.0; 208.9) compared to baseline measurement. Five patients (7%) had AMH <0.5 μg/l. In patients treated for advanced stage disease, AMH levels remained significantly lower compared to early- or intermediate stage disease, with median serum AMH of 1.3 μg/l (IQR 0.8; 2.1) after 2 years. Patients who received DECOPDAC-21 consolidation had lower AMH levels during treatment than patients receiving COPDAC-28, but the difference was no longer statistically significant at 2 years post-diagnosis. Of the 35 postmenarchal girls who did not receive hormonal co-treatment, 19 (54%) experienced treatment-induced amenorrhea, two girls had persisting amenorrhea after 2 years. LIMITATIONS, REASONS FOR CAUTION: The studied population comprises young girls with diagnosis of cHL often concurring with pubertal transition, during which AMH levels naturally rise. There was no control population, while the interpretation of AMH as a biomarker during childhood is complex. The state of cHL disease may affect AMH levels at diagnosis, potentially complicating assessment of AMH recovery as a comparison with baseline AMH. The current analysis included data up to 2-5 years post-diagnosis. WIDER IMPLICATIONS OF THE FINDINGS: The current PANCARE guideline advises to use the cyclophosphamide-equivalent dose score (CED-score, as an estimation of cumulative alkylating agent exposure) with a cut-off of 6000 mg/m2 to identify females aged <25 years at high risk of infertility. All treatment-arms of the EuroNet-PHL-C2 protocol remain below this cut-off, and based on this guideline, girls treated for cHL should therefore be considered low-risk of infertility. However, although we observed an increase in AMH after chemotherapy, it should be noted that not all girls recovered to pre-treatment AMH levels, particularly those treated for advanced stages of cHL. It remains unclear how our measurements relate to age-specific expected AMH levels and patterns. Additional (long-term) data are needed to explore clinical reproductive outcomes of survivors treated according to the EuroNet-PHL-C2 protocol. STUDY FUNDING/COMPETING INTEREST(S): The fertility add-on study was funded by the Dutch charity foundation KiKa (project 257) that funds research on all forms of childhood cancer. C.M-K., D.K., W.H.W., D.H., M.C., A.U., and A.B. were involved in the development of the EuroNet-PHL-C2 regimen. The other authors indicated no potential conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.
- MeSH
- antimülleriánský hormon * krev MeSH
- cyklofosfamid terapeutické užití aplikace a dávkování MeSH
- dítě MeSH
- Hodgkinova nemoc * krev farmakoterapie MeSH
- lidé MeSH
- mladiství MeSH
- prospektivní studie MeSH
- protokoly antitumorózní kombinované chemoterapie terapeutické užití škodlivé účinky MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
BACKGROUND: Disseminated pulmonary involvement in pediatric Hodgkin lymphoma (pHL) is indicative of Ann Arbor stage IV disease. During staging, it is necessary to assess for coexistence of non-malignant lung lesions due to infection representing background noise to avoid erroneously upstaging with therapy intensification. OBJECTIVE: This study attempts to describe new lung lesions detected on interim staging computed tomography (CT) scans after two cycles of vincristine, etoposide, prednisolone, doxorubicin in a prospective clinical trial. Based on the hypothesis that these new lung lesions are not part of the underlying malignancy but are epiphenomena, the aim is to analyze their size, number, and pattern to help distinguish true lung metastases from benign lung lesions on initial staging. MATERIALS AND METHODS: A retrospective analysis of the EuroNet-PHL-C1 trial re-evaluated the staging and interim lung CT scans of 1,300 pediatric patients with HL. Newly developed lung lesions during chemotherapy were classified according to the current Fleischner glossary of terms for thoracic imaging. Patients with new lung lesions found at early response assessment (ERA) were additionally assessed and compared to response seen in hilar and mediastinal lymph nodes. RESULTS: Of 1,300 patients at ERA, 119 (9.2%) had new pulmonary lesions not originally detectable at diagnosis. The phenomenon occurred regardless of initial lung involvement or whether a patient relapsed. In the latter group, new lung lesions on ERA regressed by the time of relapse staging. New lung lesions on ERA in patients without relapse were detected in 102 (7.8%) patients. Pulmonary nodules were recorded in 72 (5.5%) patients, the majority (97%) being<10 mm. Consolidations, ground-glass opacities, and parenchymal bands were less common. CONCLUSION: New nodules on interim staging are common, mostly measure less than 10 mm in diameter and usually require no further action because they are most likely non-malignant. Since it must be assumed that benign and malignant lung lesions coexist on initial staging, this benign background noise needs to be distinguished from lung metastases to avoid upstaging to stage IV disease. Raising the cut-off size for lung nodules to ≥ 10 mm might achieve the reduction of overtreatment but needs to be further evaluated with survival data. In contrast to the staging criteria of EuroNet-PHL-C1 and C2, our data suggest that the number of lesions present at initial staging may be less important.
- MeSH
- dítě MeSH
- doxorubicin terapeutické užití MeSH
- etoposid terapeutické užití aplikace a dávkování MeSH
- Hodgkinova nemoc * diagnostické zobrazování patologie farmakoterapie MeSH
- lidé MeSH
- mladiství MeSH
- nádory plic * diagnostické zobrazování patologie MeSH
- počítačová rentgenová tomografie * metody MeSH
- předškolní dítě MeSH
- prevalence MeSH
- prospektivní studie MeSH
- protokoly antitumorózní kombinované chemoterapie terapeutické užití MeSH
- retrospektivní studie MeSH
- staging nádorů * MeSH
- vinkristin terapeutické užití MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Výsledky klinické studie AETHERA ukázaly, že konsolidační terapie brentuximab vedotinem po vysokodávkované chemoterapii a provedení autologní transplantace kmenových hematopoetických buněk signifikantně prodlužuje přežití bez progrese u pacientů s klasickým Hodgkinovým lymfomem. V této multicentrické retrospektivní analýze sedmi hematologických center České republiky jsme analyzovali klinická data z reálné klinické praxe a výsledky léčby u 39 pacientů léčených konsolidační terapií brentuximab vedotinem od ledna 2015 do prosince 2021. Brentuximab vedotin nebyl nemocným podáván v předchozí léčbě lymfomu a pacienti měli nejméně jeden definovaný rizikový faktor pro další relaps. Medián podaných cyklů brentuximab vedotinu byl 8 (1-16), 82 % pacientů dosáhlo během léčby kompletní remise. Medián sledování byl 28 měsíců, dvouleté přežití bez progrese bylo 66,2 % (95% CI 0,52-0,85) a dvouleté celkové přežití 95 % (95% CI 0,82-1,00). Nejčastějším důvodem ukončení léčby bylo kompletní podání 16 léčebných cyklů (20,5 %), relaps/progrese lymfomu (15,4 %) a stejně tak rozvoj symptomatické periferní neuropatie, která byla v různém stupni závažnosti pozorována u 38,5 % pacientů. Naše data potvrzují deklarovanou účinnost a bezpečnost konsolidační terapie brentuximab vedotinem v reálné klinické praxi.
The results from the clinical trial AETHERA showed that consolidation therapy with brentuximab vedotin after high-dose chemotherapy followed by autologous stem cell transplantation increases progression free survival in high-risk patients with relapsed/refractory classic Hodgkin lymphoma. In this multicenter retrospective analysis from seven hematological centers in the Czech republic we have analysed real-life data of 39 patients treated between January 2015 and December 2021. Brentuximab vedotin was not administered in the previous treatment and the patients were at increased risk of subsequent lymphoma relapse with at least one defined risk factor. The median cycles of brentuximab vedotin administered was 8 (1-16), 82 % of the patients achieved complete remission during the treatment. The median follow-up was 28 months, the 2-year progression-free survival and overal survival were 66,2 % (95 % CI 0,52-0,85) and 95 % (95 % CI 0,82-1,00), respectively. The most common reason for treatment discontinuation was completion of 16 cycles administered (20,5 %) relapse/progression of the lymphoma (15,4 %) and symptomatic peripheral neuropathy as well, that was observed in various severity grades in 38,5 % patients overall. Our data have confirmed efficacy and safety of brentuximab vedotin consolidation therapy in the real-life clinical practice.
- MeSH
- brentuximab vedotin aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- chemoterapie konsolidační metody MeSH
- doba přežití bez progrese choroby MeSH
- Hodgkinova nemoc * diagnóza farmakoterapie patologie MeSH
- indukční chemoterapie metody MeSH
- klinická studie jako téma MeSH
- lidé MeSH
- nemoci periferního nervového systému etiologie MeSH
- PET/CT metody MeSH
- protinádorové látky imunologicky aktivní aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- transplantace hematopoetických kmenových buněk metody MeSH
- Check Tag
- lidé MeSH
Syndrom multiorgánové dysfunkce může být charakterizován jako kulminace excesivní generalizované imunitní, neuroendokrinní a zánětlivé reakce organismu na inzult, která postihuje minimálně dva orgánové systémy. A to i ty, které nebyly původním inzultem primárně postiženy.1 Vyskytuje se nejčastěji v souvislosti se sepsí, ale vzácně může být i projevem nádorového onemocnění. Klasický Hodgkinův lymfom je jedním z nejlépe léčitelných nádorů. V závislosti na věku, klinickém stadiu lymfomu a dalších rizikových faktorech může být vyléčeno až 90 % nemocných.2 V této kazuistice popisujeme nezvyklý průběh dlouho nepoznaného klasického Hodgkinova lymfomu, který byl asociován se syndromem aktivovaných makrofágů a vedl k bezprostředně život ohrožujícímu syndromu multiorgánové dysfunkce.
Multiple organ dysfunction syndrome can be characterized as a cumulative excessive generalized immune, neuroendocrine and inflammatory reaction of the organism on the insult that affects at least two organ systems including those, which were not primarily affected. Most often it is related to sepsis, but rarely it can be a symptom of tumor. Classic Hodgkin lymphoma is one of the best treatable tumors at all. Depending on age, clinical stage of the disease and other prognostic factors up to 90 % of the patients can be cured. In this article we describe an unusual course of the classic Hodgkin lymphoma, that was unrevealed for a long time, associated with hemophagocytic syndrome and led to the life-threatening multiple organ dysfunction syndrome.
BACKGROUND/AIM: Classic Hodgkin lymphoma (cHL) is a common B-cell malignancy. Despite the good prognosis, in some patients the standard chemotherapy and radiotherapy-based approach does not lead to long-term remission, and these patients eventually relapse. Moreover, the primary refractory disease is of major concern regarding prognosis. PATIENTS AND METHODS: We performed a retrospective analysis to evaluate PD-L1 expression in 120 patients with classic Hodgkin lymphoma (cHL). RESULTS: The median follow-up of the entire group of patients was 90 months. After initial therapy, complete remission was achieved in 113 (94.2%) patients. During the follow-up, cHL relapse/refractory disease was reported in 23 (19.2%) cases. A total of five patients died during the follow-up period, all from cHL progression. When determining PD-L1 expression on Hodgkin-Reed-Sternberg (HRS) cells, 37 cases (30.8%) were evaluated as negative, and 83 cases (69.2%) as positive. In the negative PD-L1 group of patients, no cHL relapse/refractory disease was observed during the follow-up period. However, out of 83 patients with positive PD-L1 expression on HRS cells, 23 (28%) showed relapse/refractory cHL. CONCLUSION: A significantly higher relapse rate was observed in PD-L1-positive patients diagnosed with cHL.
Dnes se Hodgkinův lymfom (HL) považuje za vyléčitelnou nemoc, protože až 90 % pacientů v časném stadiu a 70–80 % v pokročilých stadiích onemocnění dosáhne po léčbě první linie dlouhodobé remise. Přibližně 15–25 % pacientů s HL má primárně refrakterní nemoc nebo zrelabuje poté, co dosáhne odpověď po léčbě první linie. Přibližně polovina těchto nemocných je chemozenzitivních a/nebo zrelabuje po transplantaci. Vysocedávkovaná chemoterapie s autologní transplantací kmenových buněk má u pacientů s refrakterním onemocněním nebo relapsem vysokou účinnost a přispívá k dlouhodobému přežívání u významného počtu nemocných. Pacienti s vysoce rizikovým onemocněním, kteří byli léčeni načas a nedosáhli dostatečnou odpověď po standardní léčbě první linie nebo pacienti s chemozenzitivním relapsem mají dobrou prognózu. Na druhé straně, vysocedávkovaná chemoterapie následovaná autologní transplantací kmenových buněk není optimální možností u pacientů s primárně refrakterním onemocněním nebo s chemorezistentním relapsem. Alogenní transplantace krvetvorných buněk a/nebo cílená imunoterapie reprezentují léčebné možnosti pro tuto skupinu nemocných.
Today, Hodgkin lymphoma (HL) is considered a curable disease, since up to 90% of patients with early stage and 70–80% with advanced stage disease achieve long-term remission after first line treatment. Approximately 15–25% of patients with HL have primary refractory disease or relapse after responding to first line therapy. About half of these patients are diagnosed with chemosensitivity and/or relapse after transplantation. High-dose chemotherapy with autologous stem cell transplantation is highly effective in patients with refractory disease or relapse; contributing to long-term survival in a significant number of patients. Patients with high-risk disease, who were treated on time and did not achieve a sufficient response to standard first-line therapy, or patients with chemo-sensitive relapse, have a good prognosis. However, high-dose chemotherapy followed by autologous stem cell transplantation is not a well-established option in patients with primary refractory disease or with chemo-resistant relapse. Allogeneic hematopoietic cell transplant and/or targeted immunotherapy represent the options for this group of patients.
- MeSH
- brentuximab vedotin terapeutické užití MeSH
- chemorezistence * MeSH
- Hodgkinova nemoc * farmakoterapie terapie MeSH
- homologní transplantace metody MeSH
- klinická studie jako téma MeSH
- lidé MeSH
- recidiva MeSH
- transplantace hematopoetických kmenových buněk MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
BACKGROUND: Rebound thymic hyperplasia (RTH) is a common phenomenon caused by stress factors such as chemotherapy (CTX) or radiotherapy, with an incidence between 44% and 67.7% in pediatric lymphoma. Misinterpretation of RTH and thymic lymphoma relapse (LR) may lead to unnecessary diagnostic procedures including invasive biopsies or treatment intensification. The aim of this study was to identify parameters that differentiate between RTH and thymic LR in the anterior mediastinum. METHODS: After completion of CTX, we analyzed computed tomographies (CTs) and magnetic resonance images (MRIs) of 291 patients with classical Hodgkin lymphoma (CHL) and adequate imaging available from the European Network for Pediatric Hodgkin lymphoma C1 trial. In all patients with biopsy-proven LR, an additional fluorodeoxyglucose (FDG)-positron emission tomography (PET)-CT was assessed. Structure and morphologic configuration in addition to calcifications and presence of multiple masses in the thymic region and signs of extrathymic LR were evaluated. RESULTS: After CTX, a significant volume increase of new or growing masses in the thymic space occurred in 133 of 291 patients. Without biopsy, only 98 patients could be identified as RTH or LR. No single finding related to thymic regrowth allowed differentiation between RTH and LR. However, the vast majority of cases with thymic LR presented with additional increasing tumor masses (33/34). All RTH patients (64/64) presented with isolated thymic growth. CONCLUSION: Isolated thymic LR is very uncommon. CHL relapse should be suspected when increasing tumor masses are present in distant sites outside of the thymic area. Conversely, if regrowth of lymphoma in other sites can be excluded, isolated thymic mass after CTX likely represents RTH.
- MeSH
- dítě MeSH
- fluorodeoxyglukosa F18 terapeutické užití MeSH
- Hodgkinova nemoc * diagnostické zobrazování farmakoterapie komplikace MeSH
- hyperplazie thymu * diagnostické zobrazování etiologie MeSH
- lidé MeSH
- lokální recidiva nádoru diagnostické zobrazování farmakoterapie MeSH
- lymfom * farmakoterapie MeSH
- nádory brzlíku * diagnostické zobrazování farmakoterapie komplikace MeSH
- počítačová rentgenová tomografie MeSH
- pozitronová emisní tomografie metody MeSH
- radiofarmaka MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- Hodgkinova nemoc * diagnóza farmakoterapie MeSH
- lidé MeSH
- stupeň závažnosti nemoci MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Chemotherapy-related cognitive impairment (CRCI) is a well-documented side effect of cancer treatment in various types of tumors including Hodgkin's lymphoma (HL). However, a longitudinal study evaluating the cognitive performance of HL patients has been completely lacking. The aim of the study was to determine the presence of CRCI in HL patients before, promptly after, and 6 months after treatment. Thirty-six patients newly diagnosed with HL and 45 healthy controls (HC) completed the neuropsychological battery and psychological measures of affective distress and quality of life. The results indicate that HL patients have impaired performance compared to HC which cannot be explained by emotional factors. Cognitive impairments prior to treatment were found in 3 of 6 cognitive domains, i.e., verbal memory and learning, speed of processing/psychomotor speed, and abstraction/executive function. Promptly after the chemotherapy, deficits were found in the domains of memory and learning, verbal memory, speed of processing/psychomotor speed, and abstraction/executive function. Weaker cognitive performance persist even 6 months after the end of chemotherapy, specifically in domains of verbal memory and learning, and abstraction/executive function. Our results indicate the presence of cognitive impairment in HL patients already prior to treatment and increased damages caused by chemotherapy, while some of them may last for up to 6 months after the treatment.
- MeSH
- exekutivní funkce MeSH
- Hodgkinova nemoc * komplikace farmakoterapie MeSH
- kognitivní dysfunkce * chemicky indukované komplikace MeSH
- kvalita života MeSH
- lidé MeSH
- longitudinální studie MeSH
- neuropsychologické testy MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
