Peripheral T cell lymphoma
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Peripheral T cell lymphomas (PTCL) are rare in children and adolescents, and data about outcome and treatment results are scarce. The present study is a joint, international, retrospective analysis of 143 reported cases of non-anaplastic PTCL in patients <19 years of age, with a focus on treatment and outcome features. One hundred forty-three patients, between 0.3 and 18.7 years old, diagnosed between 2000 and 2015 were included in the study. PTCL not otherwise specified was the largest subgroup, followed by extranodal NK/T cell lymphoma, hepatosplenic T cell lymphoma (HS TCL), and subcutaneous panniculitis-like T cell lymphoma (SP TCL). Probability of overall survival (pOS) at 5 years for the whole group was 0.56 ± 0.05, and probability of event-free survival was (pEFS) 0.45 ± 0.05. Patients with SP TCL had a good outcome with 5-year pOS of 0.78 ± 0.1 while patients with HS TCL were reported with 5-year pOS of only 0.13 ± 0.12. Twenty-five percent of the patients were reported to have a pre-existing condition, and this group had a dismal outcome with 5-year pOS of 0.29 ± 0.09. The distribution of non-anaplastic PTCL subtypes in pediatric and adolescent patients differs from what is reported in adult patients. Overall outcome depends on the subtype with some doing better than others. Pre-existing conditions are frequent and associated with poor outcomes. There is a clear need for subtype-based treatment recommendations for children and adolescents with PTCL.
- Klíčová slova
- Non-Hodgkin’s lymphoma, Peripheral T cell lymphoma, Prognosis, Subtypes,
- MeSH
- dítě MeSH
- hodnocení výsledků zdravotní péče metody MeSH
- indukce remise MeSH
- kojenec MeSH
- kombinovaná terapie MeSH
- lidé MeSH
- mezinárodní spolupráce MeSH
- mladiství MeSH
- mladý dospělý MeSH
- periferní T-buněčný lymfom terapie MeSH
- předškolní dítě MeSH
- přežití bez známek nemoci MeSH
- protokoly protinádorové kombinované chemoterapie terapeutické užití MeSH
- retrospektivní studie MeSH
- transplantace hematopoetických kmenových buněk metody statistika a číselné údaje MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
Pediatric-type follicular (PTFL), marginal zone (MZL), and peripheral T-cell lymphoma (PTCL) account each for <2% of childhood non-Hodgkin lymphoma. We present clinical and histopathological features of PTFL, MZL, and few subtypes of PTCL and provide treatment recommendations. For localized PTFL and MZL, watchful waiting after complete resection is the therapy of choice. For PTCL, therapy is subtype-dependent and ranges from a block-like anaplastic large cell lymphoma (ALCL)-derived and, alternatively, leukemia-derived therapy in PTCL not otherwise specified and subcutaneous panniculitis-like T-cell lymphoma to a block-like mature B-NHL-derived or, preferentially, ALCL-derived treatment followed by hematopoietic stem cell transplantation in first remission in hepatosplenic and angioimmunoblastic T-cell lymphoma.
- Klíčová slova
- follicular lymphoma, marginal zone lymphoma, non-Hodgkin lymphoma, peripheral T-cell lymphoma, rare,
- MeSH
- alografty MeSH
- dítě MeSH
- folikulární lymfom * diagnóza terapie MeSH
- kojenec MeSH
- lidé MeSH
- lymfom z B-buněk marginální zóny * diagnóza terapie MeSH
- mladiství MeSH
- periferní T-buněčný lymfom * diagnóza terapie MeSH
- předškolní dítě MeSH
- transplantace hematopoetických kmenových buněk * MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND: Peripheral T-cell lymphomas (PTCLs) is a diverse group of lymphomas (10-15% of all non-Hodgkins lymphomas) with aggressive behavior. Despite the standard of 1st line anthracycline-containing regimens, clinical outcomes are poor compared to B-cell lymphomas. In addition, there are still debates about specific prognostic factors (PF) in PTCLs. AIMS: Primary endpoints - event-free survival (EFS) and overall survival (OS). To evaluate the prognostic significance of five PTCLs scores (International Prognostic Index - IPI, International Peripheral T-cell lymphoma Project Score - IPTCL, Prognostic Index for T-cell lymphoma - PIT, modified Prognostic Index for T-cell lymphoma - mPIT and T-cell score). PATIENTS AND METHODS: From 67 enrolled patients, only 50 were included: PTCL not otherwise specified (22, 44%), anaplastic large cell lymphoma ALK+ (anaplastic lymphoma kinase-positive) (10, 20%) and ALK (anaplastic lymphoma kinase-negative) (18, 36%). Patients received CHOP-like regimens (CHOP, CHOEP, EPOCH). RESULTS: The overall rate response was observed in 66% of cases (complete response 78%). There were 48% of relapses after the 1st line therapy during follow-up (median 11 months; range 1-85 months). Median age 57 (range 22-80) with male predominance 62%. In total, 40% of patients were > 60 years old, 48% had stage III-IV. Majority of patients were assessed by five prognostic scores. IPI (45 patients): the 3-year EFS and OS were higher for IPI 1 vs. IPI > 2 (80 vs. 18% and 87 vs. 27%, respectively; p = 0.0002). Receiver operating characteristic analysis confirmed poor clinical outcome to patients with PF > 1 (Se = 88 %; Sp = 68 %; AUC = 0.7; p = 0.0081). IPTCLP (41 patients): the presence of PF = 1-2 showed EFS and OS reduction. A 3-year EFS rate for 1-2 PF was 25 vs. 70% for PF = 0 (p = 0.003). Thus, 3-year OS in patients with PF = 0 vs. PF = 1-2 was 100 vs. 20% (p = 0.0001). PIT (42 patients): better 3-year EFS and OS in patients with PF = 0 vs. PF = 1-3 (88 vs. 28% and 100 vs. 34%, respectively, p = 0.001). Patients with PF = 1-3 have a higher rate of relapses vs. PF = 0 (p = 0.0005 by Cox-test). mPIT (21 patients): no significant difference between PF and clinical outcomes. T-cell score (18 patients): higher survival rates with PF 2. More than 2 PF have an impact on EFS (p = 0.005). The 3-years OS in patients with PF 2 was 77 vs. 25% in cases with PF 3 (p = 0.001). CONCLUSION: IPI, PIT, IPTCLP are still very useful in defining risk stratification. As to mPIT and T-cell score, more patients to evaluate their prognostication possibility are needed.
- Klíčová slova
- anaplastic lymphoma kinase-negative, anaplastic lymphoma kinase-positive, peripheral T-cell lymphomas, peripheral T-cell lymphomas not otherwise specified, prognostic factors,
- MeSH
- analýza přežití MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- periferní T-buněčný lymfom * farmakoterapie mortalita patologie MeSH
- prognóza MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Ukrajina MeSH
Recurrent gain-of-function mutations in the transcription factors STAT5A and much more in STAT5B were found in hematopoietic malignancies with the highest proportion in mature T- and natural killer-cell neoplasms (peripheral T-cell lymphoma, PTCL). No targeted therapy exists for these heterogeneous and often aggressive diseases. Given the shortage of models for PTCL, we mimicked graded STAT5A or STAT5B activity by expressing hyperactive Stat5a or STAT5B variants at low or high levels in the hematopoietic system of transgenic mice. Only mice with high activity levels developed a lethal disease resembling human PTCL. Neoplasia displayed massive expansion of CD8+ T cells and destructive organ infiltration. T cells were cytokine-hypersensitive with activated memory CD8+ T-lymphocyte characteristics. Histopathology and mRNA expression profiles revealed close correlation with distinct subtypes of PTCL. Pronounced STAT5 expression and activity in samples from patients with different subsets underline the relevance of JAK/STAT as a therapeutic target. JAK inhibitors or a selective STAT5 SH2 domain inhibitor induced cell death and ruxolitinib blocked T-cell neoplasia in vivo We conclude that enhanced STAT5A or STAT5B action both drive PTCL development, defining both STAT5 molecules as targets for therapeutic intervention.
- MeSH
- CD8-pozitivní T-lymfocyty metabolismus MeSH
- cytokiny MeSH
- leukemie * MeSH
- lidé MeSH
- myši MeSH
- nádorové supresorové proteiny MeSH
- periferní T-buněčný lymfom * genetika MeSH
- transkripční faktor STAT5 genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- cytokiny MeSH
- nádorové supresorové proteiny MeSH
- STAT5A protein, human MeSH Prohlížeč
- transkripční faktor STAT5 MeSH
BACKGROUND: Peripheral T-cell lymphoma, unspecified (PTCL-US) is one of the entities from the infrequent family of nodal mature T-cell lymphomas. The clinical course is aggressive, and despite multiagent chemotherapy, the median survival is about 2 years. Published data are limited to retrospective, mostly single-center studies or reviews and usually include more lymphoma subtypes. AIM: To evaluate the current treatment modalities, clinical outcome and prognostic factors in unselected, new diagnosed patients with PTCL-US in the population of the central european region (Czech Republic). METHOD: Czech Lymphoma Study Group is a national scientific organization which provides an on-line database registry which collects a data about almost all new diagnosed lymphoma patients since year 2000. All diagnostic biopsies were reviewed by a reference pathologist. RESULTS: We analyzed 63 patients with new diagnosis of PTCL-US. The median age was 59 years (25-81), chemotherapy (CHT) was administered in 56 of the 63 patients: anthracyclin-based CHT in 51%, intensive CHT in 21% and non-anthracyclin regimen was applied in 13% of the patients. The overall response rate was 74.4%, (CR in 57.4%). After a median follow-up of 19.6 months, 41% of the patients were in CR, 3.4% in PR or stable disease and 55% of the patients died. The estimated survival probability in 3 years was 36%. Clinical stage (IV) and CR achievement were found to be independent survival predictors in a multivariate analysis. CONCLUSIONS: Although the current treatment modalities are mostly ineffective in PTCL-US, appropriate intensive treatment may lead to prolonged remission but not survival.
- MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- míra přežití MeSH
- periferní T-buněčný lymfom * diagnóza mortalita terapie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: For patients with peripheral T-cell lymphoma (PTCL), outcomes using frontline treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like therapy are typically poor. The ECHELON-2 study demonstrated that brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (A+CHP) exhibited statistically superior progression-free survival (PFS) per independent central review and improvements in overall survival versus CHOP for the frontline treatment of patients with systemic anaplastic large cell lymphoma or other CD30-positive PTCL. PATIENTS AND METHODS: ECHELON-2 is a double-blind, double-dummy, randomized, placebo-controlled, active-comparator phase III study. We present an exploratory update of the ECHELON-2 study, including an analysis of 5-year PFS per investigator in the intent-to-treat analysis group. RESULTS: A total of 452 patients were randomized (1 : 1) to six or eight cycles of A+CHP (N = 226) or CHOP (N = 226). At median follow-up of 47.6 months, 5-year PFS rates were 51.4% [95% confidence interval (CI): 42.8% to 59.4%] with A+CHP versus 43.0% (95% CI: 35.8% to 50.0%) with CHOP (hazard ratio = 0.70; 95% CI: 0.53-0.91), and 5-year overall survival (OS) rates were 70.1% (95% CI: 63.3% to 75.9%) with A+CHP versus 61.0% (95% CI: 54.0% to 67.3%) with CHOP (hazard ratio = 0.72; 95% CI: 0.53-0.99). Both PFS and OS were generally consistent across key subgroups. Peripheral neuropathy was resolved or improved in 72% (84/117) of patients in the A+CHP arm and 78% (97/124) in the CHOP arm. Among patients who relapsed and subsequently received brentuximab vedotin, the objective response rate was 59% with brentuximab vedotin retreatment after A+CHP and 50% with subsequent brentuximab vedotin after CHOP. CONCLUSIONS: In this 5-year update of ECHELON-2, frontline treatment of patients with PTCL with A+CHP continues to provide clinically meaningful improvement in PFS and OS versus CHOP, with a manageable safety profile, including continued resolution or improvement of peripheral neuropathy.
- Klíčová slova
- CHOP, brentuximab vedotin, frontline treatment, overall survival, peripheral T-cell lymphoma, randomized clinical trial,
- MeSH
- antigen Ki-1 * metabolismus terapeutické užití MeSH
- brentuximab vedotin MeSH
- lidé MeSH
- periferní T-buněčný lymfom * farmakoterapie MeSH
- protokoly protinádorové kombinované chemoterapie škodlivé účinky MeSH
- vinkristin škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- antigen Ki-1 * MeSH
- brentuximab vedotin MeSH
- vinkristin MeSH
BACKGROUND: Hepatosplenic T-cell lymphoma (HSTCL) is a rare subtype of peripheral T-cell lymphoma. Patients usually present with splenomegaly and pancytopenia but without lymphadenopathy. Immunohistochemistry (IHC) staining of bone marrow biopsy shows intra-sinusoidal infiltration of CD3 and CD56 T-lymphocytes. Current treatment strategy of HSTCL includes a CHOP regimen (cyclophosphamide, adriamycine, vincristine, prednisone) followed by autologous transplantation. CASE: A 28-year-old male presented with abdominal fullness, weight loss, and massive splenomegaly. Laboratory findings revealed pancytopenia. A CT scan of the abdomen displayed hepatomegaly and massive splenomegaly. The bone marrow pathology examination showed monotonous medium-sized lymphocytes with some cluster of atypical lymphocytes with loosely condensed chromatin and pale cytoplasm. The intra-sinusoidal location was more prominent after using IHC staining of CD3 and CD56, which are characteristics of HSTCL. We administered CHOP-based regiment every 3 weeks for 3 cycles; however, the response was a stable disease. Since the splenomegaly was still massive and compromised the patient, the multidisciplinary team decided to perform splenectomy. Unfortunately, the patient did not survive the surgery. CONCLUSION: Hepatosplenic T-cell lymphoma is a rare aggressive disease, which is part of peripheral T-cell lymphoma. CHOP-based chemotherapy appeared to be ineffective, and we need further studies to find the optimal treatment of HSTCL.
- Klíčová slova
- CHOP-based chemotherapy, HSTCL, massive splenomegaly, pancytopenia,
- MeSH
- dospělí MeSH
- lidé MeSH
- lymfom T-buněčný * komplikace terapie diagnóza MeSH
- nádory jater * diagnóza MeSH
- nádory sleziny * komplikace terapie MeSH
- pancytopenie * etiologie MeSH
- periferní T-buněčný lymfom * MeSH
- splenomegalie etiologie patologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
The objective of this registry study was to analyse the outcome of patients who underwent allogeneic or autologous haematopoietic stem cell transplantation (HSCT) for hepatosplenic T-cell lymphoma (HSTL), a rare and extremely aggressive peripheral T-cell lymphoma subtype. Patients were eligible if they had histologically verified HSTL and underwent HSCT between 2003 and 2011. Seventy-six patients were identified in the European Society for Bone and Marrow Transplantation database. Additional baseline and follow-up information could be obtained from the referring centres for 36 patients. Eleven of these were excluded following histopathology review, leaving 25 patients in the final study cohort (alloHSCT 18, autoHSCT 7). With a median follow-up of 36 months, 2 patients relapsed after alloHSCT, resulting in a 3-year progression-free survival of 48%. After autoHSCT, 5 patients relapsed and subsequently died. This study indicates that graft-versus-lymphoma activity conferred by alloHSCT can result in long-term survival for a substantial proportion of patients with HSTL.
- MeSH
- analýza přežití MeSH
- autologní transplantace MeSH
- databáze faktografické MeSH
- dospělí MeSH
- homologní transplantace MeSH
- kooperační chování MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- nádory jater mortalita patologie terapie MeSH
- nádory sleziny mortalita patologie terapie MeSH
- následné studie MeSH
- periferní T-buněčný lymfom mortalita patologie terapie MeSH
- recidiva MeSH
- registrace * MeSH
- retrospektivní studie MeSH
- senioři MeSH
- transplantace hematopoetických kmenových buněk * MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Evropa MeSH
BACKGROUND: Nodal peripheral T-cell lymphomas (PTCLs) are infrequent subtypes of non-Hodgkin's lymphomas. The WHO classification recognizes three subgroups of nodal PTCL: peripheral T-cell lymphoma not otherwise specified (PTCL, NOS), anaplastic large cell lymphoma (ALCL) and angioimmunoblastic lymphoma (AIL). The clinical course is aggressive and despite multiagent chemotherapy, the median survival is about 2 years. Optimal first-line chemotherapy is not established and the role of high-dose therapy with autologous stem cell support is still controversial. AIM: To analyze the long-term outcome of PTCL patients treated with intensive first-line chemotherapy with highdose therapy and autologous transplant consolidation. METHOD: Sequential chemotherapy protocol consisting of 3 cycles of CHOEP-21-like regimen (PACEBO), 1 cycle of an ifosfamide and methotrexate-based regimen (IVAM) and a priming regimen with high-dose cytosine arabinoside (HAM). Consolidation was provided with myeloablative conditioning (BEAM 200) and autologous stem cell support. Eighty-four patients with aggressive high-risk lymphoma were treated with the sequential protocol from 2000 to 2007 in our institution. Here we report our experience with 18 patients with nodal PTCL (10 PTCL, NOS; 3 ALCL, ALKnegative; 2 ALCL, ALK-positive; 2 ALCL, unknown ALK status; 1 AIL). RESULTS: Eleven (61 %) patients achieved complete remission, 3 (17 %) partial remission and 4 (22 %) patients failed the procedure. The overall response rate was 77.8 %. After a median follow-up of 25.7 months, nine patients relapsed or progressed (6 PTCL, NOS; 2 ALCL ALK-positive; 1 ALCL ALK-negative; median 14.1 months) and four patients died (lymphoma progression). The relapse was treated with allogeneic stem transplantation in one patient. The 2-year progression-free survival (PFS) was 52 % (95 % CI, 0.27 to 0.76); the 2-year overall survival rate reached 71 % (95 % CI, 0.47 to 0.95). CONCLUSION: Our results show that intensive first-line chemotherapy with high-dose therapy and autologous transplant consolidation offers a chance for long-term survival in patients with chemosensitive PTCL.
- MeSH
- dospělí MeSH
- homologní transplantace MeSH
- kombinovaná terapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- míra přežití MeSH
- periferní T-buněčný lymfom mortalita terapie MeSH
- přežití bez známek nemoci MeSH
- protokoly protinádorové kombinované chemoterapie terapeutické užití MeSH
- senioři MeSH
- transplantace hematopoetických kmenových buněk * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Peripheral T-cell lymphomas (PTCL) are infrequent subtypes of non-Hodgkin's lymphomas. The clinical course is aggressive and the median survival is about 2-3 years. An optimal first-line chemotherapy protocol has not been established and the role of high-dose therapy with autologous stem cell transplantation (ASCT) is still unclear. AIM: To analyze the long-term outcome of unselected PTCL patients treated with intensive first-line chemotherapy with high-dose therapy and ASCT. METHOD: Here we report our experience with 29 patients with PTCL. The histological subtypes were as follows: peripheral T-cell lymphoma, not otherwise specified n=13; anaplastic large cell lymphoma (ALCL) ALK-negative n=5; ALCL ALK-positive n=3; ALCL with an unknown ALK status n=3; angioimmunoblastic lymphoma n=1; hepatosplenic lymphoma n=1; Sézary syndrome n=1; and enteropathy-associated T-cell lymphoma n=2. The median age at diagnosis was 48 years (29-64), most patients had advanced Ann Arbor stages (22 patients, 77%), IPI score ≥3 was found in 13 (45%) and PIT score ≥2 in 17 (59%) of the 29 patients. Eighteen patients received first-line high-dose therapy and autologous SCT consolidation; two patients were consolidaed with allogeneic SCT in the 1st complete remission and one patient in the 1st relapse. Ten patients with FDG-avid lymphoma were examined with integrated Positron emission tomography/ Computed tomography (PET/CT) at the time of diagnosis and after first-line therapy, two other patients were assessed with Positron emission tomography/ Computed tomography (PET/CT) only at time of restaging. RESULTS: Nineteen (66%) patients achieved complete remission, 3 (10%) partial remission and 7 (24%) patients failed the treatment. The overall response rate was 76%. PET negativity (complete metabolic response) after therapy was achieved in 8/12 (75%) individuals. After a median follow-up of 55.1 months, 14 (48.3%) patients relapsed or progressed and nine patients died (lymphoma progression). Eleven patients (50% of chemosensitive patients) survived more than 50 months. Three of the long-term survivors were treated with allogeneic SCT. The 2-year event-free survival (EFS) was 52% (95% confidence interval [CI], 0.33-0.71); the 2-year overall survival (OS) rate reached 65% (95%CI, 0.47-0.84). PET negativity was associated with a lower probability of relapse (chi-square p=0.09). CONCLUSION: Our data show that intensive first-line therapy with etoposide-doxorubicine-based regimens and ASCT consolidation may lead to long-term disease control in about a half of patients with chemosensitive PTCL. Achievement PET negativity is probably an essential prerequisite for long-term complete remission.
- MeSH
- dospělí MeSH
- indukce remise MeSH
- kombinovaná terapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- míra přežití MeSH
- periferní T-buněčný lymfom diagnostické zobrazování farmakoterapie mortalita terapie MeSH
- pozitronová emisní tomografie MeSH
- protokoly protinádorové kombinované chemoterapie terapeutické užití MeSH
- transplantace hematopoetických kmenových buněk MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH