Primární pyomyozitida je hnisavá infekce kosterního svalu často s tvorbou abscesů, která vzniká na základě hematogenní infekce. Primární infekce má obvykle subakutní začátek a nejčastěji postihuje jednu svalovou skupinu dolní končetiny nebo svaly kyčle a pánve. Prezentujeme 16letého diabetika I. typu s nově diagnostikovanou akutní lymfoblastickou leukemií. Agresivní indukční chemoterapie byla šestý den komplikována febrilní neutropenií. Pacient udával při chůzi bolest pravého adduktoru stehna, na kůži jsme pozorovali flegmonózní změny kůže, připomínající podkožní hematom. Shrnujeme diagnostické a léčebné postupy, které vedly k dosažení definitivní diagnózy a terapeutického úspěchu.

Primary pyomyositis is a purulent infection of the skeletal muscle often with abscess formation, which arises from a haematogenous infection. Primary infections usually have a subacute onset and most commonly affect one muscle group of the lower limb or the muscles of the hip and pelvis. We present a 16-year-old type I diabetic with with newly diagnosed acute lymphoblastic leukemia. Aggressive induction chemotherapy was complicated by febrile neutropenia on day 6. The patient reported right thigh adductor pain on walking, and we observed phlegmonous skin changes resembling a subcutaneous hematoma. We summarize the diagnostic and therapeutic procedures that led to a definitive diagnosis and therapeutic success.

• MeSH
• akutní lymfatická leukemie * komplikace   MeSH
• antibakteriální látky aplikace a dávkování   terapeutické užití   MeSH
• diabetes mellitus 1. typu MeSH
• drenáž MeSH
• lidé MeSH
• mladiství MeSH
• pyomyozitida * diagnóza   etiologie   farmakoterapie   MeSH
• rizikové faktory MeSH
• Staphylococcus aureus izolace a purifikace   patogenita   MeSH
• stehno diagnostické zobrazování   patologie   MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

In children with acute lymphoblastic leukemia (ALL), risk groups for invasive fungal disease (IFD) with need for antifungal prophylaxis are not well characterized, and with the advent of new antifungal compounds, current data on outcome are scarce. Prospectively captured serious adverse event reports of children enrolled in the international, multi-center clinical trial AIEOP-BFM ALL2009 were screened for proven/probable IFD, defined according to the updated EORTC/MSG consensus definitions. In a total of 6136 children (median age 5.2 years), 224 proven/probable IFDs (65 yeast and 159 mold) were reported. By logistic regression, the risk for proven/probable IFDs was significantly increased in children ≥12 years and those with a blast count ≥10% in the bone marrow on day 15 (P < 0.0001 each). Proven/probable IFDs had a 6-week and 12-week mortality of 10.7% and 11.2%, respectively. In the multivariate analysis, the hazard ratio for event-free and overall survival was significantly increased for proven/probable IFD, age ≥12 years, and insufficient response to therapy (P < 0.001, each). Our data define older children with ALL and those with insufficient treatment-response at high risk for IFD. As we show that IFD is an independent risk factor for event-free and overall survival, these patients may benefit from targeted antifungal prophylaxis.

• MeSH
• akutní lymfatická leukemie * komplikace   farmakoterapie   MeSH
• antifungální látky terapeutické užití   MeSH
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mykózy * farmakoterapie   etiologie   MeSH
• předškolní dítě MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• předškolní dítě MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• práce podpořená grantem MeSH

Although initial central nervous system (CNS) involvement is rarely detected in childhood acute lymphoblastic leukemia (ALL), risk-adapted CNS-directed therapy is essential for all patients. Treatment intensity depends on the initial CNS status. In the AIEOP-BFM ALL 2009 trial, patients with cytomorphologic detection of leukemic blasts in initial cerebrospinal fluid were classified as CNS2 or CNS3 and received five intrathecal doses of methotrexate (MTX) in induction therapy compared to patients with CNS1 status (no blasts detected) who received three doses. The impact of additional intrathecal (IT) MTX on systemic toxicity in induction therapy is unknown. Between June 1st 2010 and February 28th 2017, a total of 6,136 ALL patients aged 1-17 years were enrolled onto the AIEOP-BFM ALL 2009 trial. The effect of three versus five doses of IT MTX during induction therapy on the incidence of severe infectious complications was analyzed. Among 4,706 patients treated with three IT MTX doses, 77 (1.6%) had a life-threatening infection during induction as compared to 59 of 1,350 (4.4%) patients treated with five doses (P<0.001; Odds Ratio 2.86 [95% Confidence Interval 1.99-4.13]). In a multivariate regression model, treatment with additional IT MTX proved to be the strongest risk factor for life-threatening infections (Odds Ratio 2.85 [1.96-4.14]). Fatal infections occurred in 16 (0.3%) and 38 (1.6%) patients treated with three or five IT MTX doses, respectively (P<0.001). As the relevance of additional intrathecal MTX in induction for relapse prevention in CNS2 patients is unclear, doses of intrathecal therapy have been reduced for these patients. (Clinicaltrials.gov identifiers: NCT01117441 and NCT00613457).

• MeSH
• akutní lymfatická leukemie * komplikace   farmakoterapie   MeSH
• dítě MeSH
• indukční chemoterapie škodlivé účinky   MeSH
• kombinovaná terapie MeSH
• lidé MeSH
• methotrexát * terapeutické užití   MeSH
• protokoly antitumorózní kombinované chemoterapie škodlivé účinky   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• akutní lymfatická leukemie * diagnóza   komplikace   MeSH
• bolesti zad etiologie   MeSH
• COVID-19 komplikace   MeSH
• horečka etiologie   MeSH
• leukopenie etiologie   MeSH
• lidé MeSH
• mladiství MeSH
• syndrom systémové zánětlivé reakce * etiologie   komplikace   MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

The development of a second malignancy after the diagnosis of childhood acute lymphoblastic leukemia (ALL) is a rare event. Certain second malignancies have been linked with specific elements of leukemia therapy, yet the etiology of most second neoplasms remains obscure and their optimal management strategies are unclear. This is a first comprehensive report of non-Hodgkin lymphomas (NHLs) following pediatric ALL therapy, excluding stem-cell transplantation. We analyzed data of patients who developed NHL following ALL diagnosis and were enrolled in 12 collaborative pediatric ALL trials between 1980-2018. Eighty-five patients developed NHL, with mature B-cell lymphoproliferations as the dominant subtype (56 of 85 cases). Forty-six of these 56 cases (82%) occurred during or within 6 months of maintenance therapy. The majority exhibited histopathological characteristics associated with immunodeficiency (65%), predominantly evidence of Epstein-Barr virus-driven lymphoproliferation. We investigated 66 cases of post-ALL immunodeficiency-associated lymphoid neoplasms, 52 from our study and 14 additional cases from a literature search. With a median follow-up of 4.9 years, the 5-year overall survival for the 66 patients with immunodeficiency-associated lymphoid neoplasms was 67.4% (95% confidence interval [CI], 56-81). Five-year cumulative risks of lymphoid neoplasm- and leukemia-related mortality were 20% (95% CI, 10.2-30) and 12.4% (95% CI, 2.7-22), respectively. Concurrent hemophagocytic lymphohistiocytosis was associated with increased mortality (hazard ratio, 7.32; 95% CI, 1.62-32.98; P = .01). A large proportion of post-ALL lymphoid neoplasms are associated with an immunodeficient state, likely precipitated by ALL maintenance therapy. Awareness of this underrecognized entity and pertinent diagnostic tests are crucial for early diagnosis and optimal therapy.

• MeSH
• akutní lymfatická leukemie * terapie   komplikace   MeSH
• dítě MeSH
• infekce virem Epsteina-Barrové * komplikace   diagnóza   MeSH
• lidé MeSH
• lymfom * komplikace   MeSH
• nehodgkinský lymfom * patologie   MeSH
• sekundární malignity * MeSH
• virus Epsteinův-Barrové MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: The outcome of infants with KMT2A-germline acute lymphoblastic leukaemia (ALL) is superior to that of infants with KMT2A-rearranged ALL but has been inferior to non-infant ALL patients. Here, we describe the outcome and prognostic factors for 167 infants with KMT2A-germline ALL enrolled in the Interfant-06 study. METHODS: Univariate analysis on prognostic factors (age, white blood cell count at diagnosis, prednisolone response and CD10 expression) was performed on KMT2A-germline infants in complete remission at the end of induction (EOI; n = 163). Bone marrow minimal residual disease (MRD) was measured in 73 patients by real-time quantitative polymerase chain reaction at various time points (EOI, n = 68; end of consolidation, n = 56; and before OCTADAD, n = 57). MRD results were classified as negative, intermediate (<5∗10-4), and high (≥5∗10-4). RESULTS: The 6-year event-free and overall survival was 73.9% (standard error [SE] = 3.6) and 87.2% (SE = 2.7). Relapses occurred early, within 36 months from diagnosis in 28 of 31 (90%) infants. Treatment-related mortality was 3.6%. Age <6 months was a favourable prognostic factor with a 6-year disease-free survival (DFS) of 91% (SE = 9.0) compared with 71.7% (SE = 4.2) in infants >6 months of age (P = 0.04). Patients with high EOI MRD ≥5 × 10-4 had a worse outcome (6-year DFS 61.4% [SE = 12.4], n = 16), compared with patients with undetectable EOI MRD (6-year DFS 87.9% [SE = 6.6], n = 28) or intermediate EOI MRD <5 × 10-4 (6-year DFS 76.4% [SE = 11.3], n = 24; P = 0.02). CONCLUSION: We conclude that young age at diagnosis and low EOI MRD seem favourable prognostic factors in infants with KMT2A-germline ALL and should be considered for risk stratification in future clinical trials.

• MeSH
• akutní lymfatická leukemie komplikace   mortalita   patologie   MeSH
• analýza přežití MeSH
• kojenec MeSH
• lidé MeSH
• prognóza MeSH
• reziduální nádor etiologie   patologie   MeSH
• výsledek terapie MeSH
• zárodečné buňky MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Optimal conditioning for adults with acute lymphoblastic leukemia (ALL) treated with haploidentical hematopoietic cell transplantation (haplo-HCT) and post-transplant cyclophosphamide has not been established so far. We retrospectively compared outcomes for two myeloablative regimens: fludarabine + total body irradiation (Flu-TBI, n = 117) and thiotepa + iv. busulfan + fludarabine (TBF, n = 119). Patients transplanted either in complete remission (CR) or with active disease were included in the analysis. The characteristics of both groups were comparable except for patients treated with TBF were older. In univariate analysis the incidence of non-relapse mortality (NRM) at 2 years was increased for TBF compared to Flu-TBI (31% vs. 19.5%, p = 0.03). There was a tendency towards reduced incidence of relapse after TBF (p = 0.11). Results of multivariate analysis confirmed a reduced risk of NRM using Flu-TBI (HR = 0.49, p = 0.03). In the analysis restricted to patients treated in CR1 or CR2, the use of Flu-TBI was associated with a decreased risk of NRM (HR = 0.34, p = 0.009) but an increased risk of relapse (HR = 2.59, p = 0.01) without significant effect on survival and graft-versus-host disease. We conclude that for haplo-HCT recipients with ALL, Flu-TBI may be preferable for individuals at high risk of NRM while TBF should be considered in cases at high risk of relapse.

• MeSH
• akutní lymfatická leukemie * komplikace   terapie   MeSH
• akutní myeloidní leukemie * terapie   MeSH
• busulfan škodlivé účinky   MeSH
• celotělové ozáření škodlivé účinky   MeSH
• dospělí MeSH
• lidé MeSH
• nemoc štěpu proti hostiteli * etiologie   MeSH
• příprava pacienta k transplantaci metody   MeSH
• recidiva MeSH
• retrospektivní studie MeSH
• thiotepa škodlivé účinky   MeSH
• transplantace hematopoetických kmenových buněk * škodlivé účinky   MeSH
• vidarabin analogy a deriváty   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Akutní lymfoblastická leukemie (ALL) je nejčastějším maligním nádorovým onemocněním v dětském věku. Léčba ALL je založena na kombinované chemoterapii. Trvalého vyléčení lze v dnešní době dosáhnout až u 90 % pacientů. Onemocnění často doprovází řada komplikací. Mezi nejčastější komplikace patří bakteriální a mykotické infekce způsobené běžnými i oportunními patogeny. Mykotické infekce tvoří až 40 % všech infekčních komplikací. Prezentujeme případ dvouletého děvčátka asijského původu s projevy invazivní kandidózy diagnostikované během indukční fáze léčby ALL komplikovaného život ohrožujícím multiorgánovým selháním.

Acute lymphoblastic leukemia (ALL) represents 25 % of childhood tumors and it ́s the most frequent cancer in children. ALL treatment is based on combined chemotherapy. Long-lasted treatment is now achieved in up to 90 % of patients. The disease is accompanied by a number of complications. The most prevalent complications include bacterial and fungal infections caused by common and opportunistic pathogens. Fungal infections make up 40 % of all infectious complications. We present the case of a 2year-old girl of Asian origin with manifestations of invasive candidiasis diagnosed during the induction phase of treatment of ALL complicated by life-threatening multiorgan failure.

• MeSH
• akutní lymfatická leukemie * diagnóza   farmakoterapie   komplikace   MeSH
• antibakteriální látky terapeutické užití   MeSH
• antifungální látky terapeutické užití   MeSH
• bakteriemie farmakoterapie   MeSH
• fungemie farmakoterapie   MeSH
• kandidóza invazivní * diagnóza   farmakoterapie   MeSH
• kombinovaná farmakoterapie metody   MeSH
• lidé MeSH
• multiorgánové selhání terapie   MeSH
• předškolní dítě MeSH
• progrese nemoci MeSH
• Check Tag
• lidé MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

Osteonekróza (ON) je významnou komplikací agresivní chemoterapie u dětí a dospívajících s akutní lymfoblastickou leukemií (ALL). Představujeme 13letého chlapce s ALL, u kterého došlo v průběhu udržovací léčby ke komplikaci ON obou tibií a talů. Podle kritérií protokolu AIEOP‑BFM ALL 2009 mu byla diagnostikována vysoce riziková ALL. V průběhu udržovací léčby (59. týden) si začal stěžovat na bolest kolem obou kotníků. Vyšetření pomocí magnetické rezonance prokázala ON obou tibií a talů. Chůze bez zátěže po dobu jednoho roku vedla ke stabilizaci osteonekrotických ložisek. U pacienta jsme prokázali většinu nedávno identifikovaných rizikových faktorů pro ON, včetně vyšší kumulativní dávky glukokortikoidů (GC), věk nad 10 let, kombinovanou léčbu dexametazonem a PEG‑L- asparaginázou a dlouhotrvající působení hyperlipidemie.

Osteonecrosis (ON) is a significant complication of aggressive chemotherapy in children and adolescents with acute lymphoblastic leukemia (ALL). We present a 13-year-old- boy with ALL complicated during maintenance therapy by ON of bilateral tibiae and tali. He was dignosed as having high risk ALL according to the criteria of AIEOP-BFM ALL 2009 protocol. During maintenance treatment (week 59), he began complaining of pain around both ankles. Magnetic resonance imaging study demonstrated osteonecroses of bilateral tibiae and tali. Nonweight-bearing over 1 year led to stabilization of osteonecrotic lesions. He had most of the recently identified risk factors for ON, including higher cumulative dose of glucocorticosteroids (GC), age over 10 years, treatment with combination of dexamethasone and PEG-L-asparaginase and prolonged exposure to hyperlipidemia.

• MeSH
• akutní lymfatická leukemie * farmakoterapie   komplikace   MeSH
• asparaginasa škodlivé účinky   MeSH
• dexamethason škodlivé účinky   MeSH
• dítě MeSH
• glukokortikoidy škodlivé účinky   MeSH
• hlezenní kloub diagnostické zobrazování   účinky léků   MeSH
• hyperlipidemie komplikace   MeSH
• lidé MeSH
• osteonekróza * chemicky indukované   etiologie   terapie   MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

PURPOSE: Infant acute lymphoblastic leukemia (ALL) is characterized by a high incidence of KMT2A gene rearrangements and poor outcome. We evaluated the value of minimal residual disease (MRD) in infants with KMT2A-rearranged ALL treated within the Interfant-06 protocol, which compared lymphoid-style consolidation (protocol IB) versus myeloid-style consolidation (araC, daunorubicin, etoposide/mitoxantrone, araC, etoposide). MATERIALS AND METHODS: MRD was measured in 249 infants by DNA-based polymerase chain reaction of rearranged KMT2A, immunoglobulin, and/or T-cell receptor genes, at the end of induction (EOI) and end of consolidation (EOC). MRD results were classified as negative, intermediate (< 5 × 10-4), and high (≥ 5 × 10-4). RESULTS: EOI MRD levels predicted outcome with 6-year disease-free survival (DFS) of 60.2% (95% CI, 43.2 to 73.6), 45.0% (95% CI, 28.3 to 53.1), and 33.8% (95% CI, 23.8 to 44.1) for infants with negative, intermediate, and high EOI MRD levels, respectively (P = .0039). EOC MRD levels were also predictive of outcome, with 6-year DFS of 68.2% (95% CI, 55.2 to 78.1), 40.1% (95% CI, 28.1 to 51.9), and 11.9% (95% CI, 2.6 to 29.1) for infants with negative, intermediate, and high EOC MRD levels, respectively (P < .0001). Analysis of EOI MRD according to the type of consolidation treatment showed that infants treated with lymphoid-style consolidation had 6-year DFS of 78.2% (95% CI, 51.4 to 91.3), 47.2% (95% CI, 33.0 to 60.1), and 23.2% (95% CI, 12.1 to 36.4) for negative, intermediate, and high MRD levels, respectively (P < .0001), while for myeloid-style-treated patients the corresponding figures were 45.0% (95% CI, 23.9 to 64.1), 41.3% (95% CI, 23.2 to 58.5), and 45.9% (95% CI, 29.4 to 60.9). CONCLUSION: This study provides support for the idea that induction therapy selects patients for subsequent therapy; infants with high EOI MRD may benefit from AML-like consolidation (DFS 45.9% v 23.2%), whereas patients with low EOI MRD may benefit from ALL-like consolidation (DFS 78.2% v 45.0%). Patients with positive EOC MRD had dismal outcomes. These findings will be used for treatment interventions in the next Interfant protocol.

• MeSH
• akutní lymfatická leukemie komplikace   MeSH
• lidé MeSH
• prognóza MeSH
• reziduální nádor etiologie   patofyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH