Диссеминированный мукормикоз у больного острым лимфобластным лейкозом (клинический случай)

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МУКОРМИКОЗ У ДЕТЕЙ С ГЕМАТОЛОГИЧЕСКИМИ И ОНКОЛОГИЧЕСКИМИ ЗАБОЛЕВАНИЯМИ В САНКТ-ПЕТЕРБУРГЕ

In prospective multicenter study were included 20 pediatriconcohematologic patients with mucormycosis. Age: 3 – 17 yy (median – 11), females – 60%. The diagnosiswas made according to EORTC/MSG 2008 criteria (post mortem – 25%). The main underlying disease was acutel eukemia (70%), risk factors – prolong severe neutropenia (median – 31 d) and lymphocytopenia (median – 33 d) after cytostatic chemotherapy or hematopoietic stem cells transplantation. Etiology agents were Lichtheimia corуmbifera, Rhizopus spp. and Rhizomucor spp. Main sites of infection were lungs (65%) and paranasal synuses (30%), dissemination – 45%. Antifungal therapy (amphotericin B lipid coplex, posaconazole, caspofungin, amphotericin B) was used in 75% patients, surgery – 30%. Overall mortality in 12 weeks was 70%.В проспективное многоцентровое исследование включили 20 детей с гематологическими и онкологическими заболеваниями, осложнившимися мукормикозом. Возраст – от 3 до 17 лет (медиана – 11 лет), девочки – 60%. Диагноз мукормикоза был установлен согласно критериям EORTC/MSG, 2008 (post mortem – 25%). Установлено, что мукормикоз развивается преимущественно у больных острым лейкозом (70%), на фоне длительного агранулоцитоза (медиана – 31 день) и лимфоцитопении (медиана – 33 дня) после интенсивной цитостатической и/или иммуносупрессивной терапии, а также трансплантации гемопоэтических стволовых клеток. Возбудители: Lichtheimia corуmbifera, Rhizopus spp. и Rhizomucor spp. Заболевание начинается с поражения легких (65%) и придаточных пазух носа (30%), диссеминацию выявили у 45% пациентов. Антимикотическую терапию (липидный комплекс амфотерицина В, позаконазол, каспофунгин, амфотерицин В) проводили 75% больных, хирургическое лечение – 30%. Общая летальность в течение 12 недель составила 70%

COVID-19 infection in adult patients with hematological malignancies: a European Hematology Association Survey (EPICOVIDEHA)

Background: Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. Methods: The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. Results: The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March–May 2020) and the second wave (October–December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value < 0.0001). In the multivariable analysis, age, active malignancy, chronic cardiac disease, liver disease, renal impairment, smoking history, and ICU stay correlated with mortality. Acute myeloid leukemia was a higher mortality risk than lymphoproliferative diseases. Conclusions: This survey confirms that COVID-19 patients with HM are at high risk of lethal complications. However, improved COVID-19 prevention has reduced mortality despite an increase in the number of reported cases.EPICOVIDEHA has received funds from Optics COMMITTM (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020-8223)

Mucormycosis in children with hematological and oncological diseases in saint-petersburg

In prospective multicenter study were included 20 pediatriconcohematologic patients with mucormycosis. Age: 3 – 17 yy (median – 11), females – 60%. The diagnosiswas made according to EORTC/MSG 2008 criteria (post mortem – 25%). The main underlying disease was acutel eukemia (70%), risk factors – prolong severe neutropenia (median – 31 d) and lymphocytopenia (median – 33 d) after cytostatic chemotherapy or hematopoietic stem cells transplantation. Etiology agents were Lichtheimia corуmbifera, Rhizopus spp. and Rhizomucor spp. Main sites of infection were lungs (65%) and paranasal synuses (30%), dissemination – 45%. Antifungal therapy (amphotericin B lipid coplex, posaconazole, caspofungin, amphotericin B) was used in 75% patients, surgery – 30%. Overall mortality in 12 weeks was 70%

COMBINATION OF INVASIVE ASPERGILLOSIS AND MUCORMYCOSIS IN ONCOHEMATOLOGICAL PATIENTS

Objective. Data analysis of the register of patients with invasive aspergillosis (IA), which was founded in Saint Petersburg (1998–2017), and clinical case description of successful treatment of IA and mucormycosis with lungs involvement in a patient with Hodgkin’s lymphoma.Materials and methods. In the study were included 29 oncohematological patients with IA and mucormycosis. In control group were included 483 oncohematological patients with IA. We used criteria EORTS/MSG, 2008 for IA and mucormycosis diagnosis.Results. We identified that the combination of IA and mucormycosis significantly often develops in patients with acute lymphoblastic leukemia (32 %, р = 0.001), and allogeneic hematopoietic stem cells transplants (allo-HSCT) recipients (52 %, р = 0.001). In mixed-infection Aspergillus nidulans was frequent IA etiological agent (11 %, р = 0.001). The main mucormycosis etiological agents were Rhizopus spp. (45 %), Lichtheimia corуmbifera (20 %). The main sites of the localization were lungs (76 %), disseminated process and paranasal sinuses involvement were identified more frequently (45 % and 17 % (р = 0.0001; р = 0.002), respectively). Typical clinical feature of IA and mucormycosis combinations was hemoptysis (24 %, р = 0.008), radiological signs – lesions with cavities destruction (38 %), hydrothorax (29 %) and a “reverse halo” symptom (17 %). Antifungal therapy received 76 % of patients, surgery – 34 %.Conclusion. Mucormycosis was revealed in 5.7 % of patients with IA. The main risk factors for co-infection are allo-HSCT, long-term agranulocytosis, lymphocytopenia and glucocorticosteroid therapy. Overall 12 weeks survival in patients with mixed-infection was 38 %, significantly lower than in patients with IA (р = 0.005). An unfavorable prognosis factor was dissemination of mycotic infection (р = 0.009)

INVASIVE ASPERGILLOSIS AND MUCORMYCOSIS IN ONCOHEMATOLOGICAL PATIENTS

In the retrospective multicenter study during 2007–2017 we included 59 oncohematological patients with mucormycosis and 541 patients with invasive aspergillosis. Our study showed that mucomorhycosis more often developed in children and adolescents (p = 0.001), and after «graft versus host» disease development (p = 0.0001). Patients with mucormycosis were more immunosuppressed: severe neutropenia was in 88 % vs. 82 %, median duration of neutropenia ‒ 30 days vs. 14 days, p = 0.0001, lymphocytopenia – 77 % vs. 65 %, median duration of lymphocytopenia – 25 days vs. 14 days, p = 0.001. The main sites of infection were lungs, nevertheless in patients with mucormycosis it was less frequent (73 % vs. 97 %, p = 0.02), but more frequent were ≥2 organs involvement (42 % vs. 8 %, p = 0.001) and paranasal sinuses involvement (15 % vs. 6 %, p = 0.04). Typical clinical features of mucomorhycosis were localized pain syndrome (53 % vs. 5 %, p = 0.0001), hemoptysis (32 % vs. 6 %, p = 0.001), on lung computed tomography scan – pleural effusion (53 % vs. 7 %, p = 0.003), lesions with destruction (38 % vs. 8 %, p = 0.0001) and “a reverse halo” symptom (17 % vs. 3 %). The overall 12-week survival was significantly lower in patients with mucormycosis (49 % vs. 81 %, p = 0.0001). In both groups unfavorable prognosis factors were: ≥2 organs involvement (p = 0.0009) and concomitant bacterial or viral infection (p = 0.001 and p = 0.008 respectively). In mucormycosis patients favorable prognosis factor was remission of underlying disease (p = 0.006), in invasive aspergillosis patients – early bronchoscopy (p = 0.003), voriconazole use (p = 0.0007) and secondary antifungal prophylaxis (p = 0.0001)

Invasive aspergillosis: results of multicenter study

<p>We present the results of a multicenter study of 445 patients with “proven” and “probable” invasive aspergillosis (EORTC/MSG, 2008). Invasive aspergillosis usually occurs in patients with hematological malignancies (88 %), main underlying diseases were acute myeloid and acute lymphoblastic leukemia. The risk factors: prolonged agranulocytosis (64 %), cytostatic chemotherapy (57 %), corticosteroid treatment (45 %), and allogeneic hematopoietic stem cells transplantation (29 %). The pathogens – A. fumigatus (42 %), A. niger (33 %), and A. flavus (21 %). The main site of infection were lungs (86 %). 12 week overall survival was 83 %. Bronchoscopy use for the early diagnosis (p = 0.01), adequate<br />therapy with voriconazole (p = 0.002) and secondary antifungal prophylaxis (p = 0.0003) were positive prognostic factors for survival of patients with invasive aspergillosis.</p

MUCORMYCOSIS IN ONCOHEMATOLOGY PATIENTS (results of the prospective study)

In 2004–2016 we prospectively observed 59 oncohematology patients with mucormycosis; 21 children and 38 adults. The most frequent underlying diseases were acute myeloid leukemia and acute lymphoblastic leukemia (64 %); and main risk factors were сytostatic chemotherapy and allogeneic HSCT with prolonged (median – 30 days) neutropenia and lymphocytopenia. The etiology agents were Rhizopus spp. (47 %); Rhizomucor spp. (28 %); Lichtheimia corуmbifera (17 %) and Mucor spp. (8 %). Lichtheimia corуmbifera was found more often in children; Rhizopus and Mucor spp. in adults. Pulmonary mucormycosis was main clinical form (73 %); and ≥2 organs involvement was noted in 44 % patients. Antifungal therapy was used in 78 % patients; surgery – in 47 %. In treated with antifungals patients 12 weeks overall survival was 59 %. The positive prognostic factors were remission of underlying disease and combination antifungal therapy