Infectious Complications after Haploidentical Hematopoietic Stem Cells Transplantation in Patients with High-Risk Tumors of Hematopoietic and Lymphoid Tissues: A Single-Center Experience

YuS Osipov1, SS Bessmeltsev2, GN Salogub1, VV Ivanov1, ES Mikhailov1, NA Zhukova1, AV Chechetkin2

1 VA Almazov National Medical Research Center, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341

2 Russian Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

For correspondence: Yurii Sergeevich Osipov, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341; Tel.: +7(812)702-37-65; e-mail: osipov_yus@almazovcentre.ru

For citation: Osipov YuS, Bessmeltsev SS, Salogub GN, et al. Infectious Complications after Haploidentical Hematopoietic Stem Cells Transplantation in Patients with High-Risk Tumors of Hematopoietic and Lymphoid Tissues: A Single-Center Experience. Clinical oncohematology. 2019;12(4):406–15 (In Russ).

DOI: 10.21320/2500-2139-2019-12-4-406-415


ABSTRACT

Aim. To determine the incidence of viral, bacterial, and fungal infections in post-transplant period and to assess the prognostic value of infections and their influence on early and long-term results of haploidentical hematopoietic stem cells transplantation (haplo-HSCT).

Materials & Methods. Retrospective study included 61 patients older than 18 years with high-risk oncohematological diseases. In the period from 2015 to 2018 all patients received haplo-HSCT. Median follow-up after haplo-HSCT was 12.5 months (376 days, range 6–1202). Patients were divided into two groups. The first group (n = 26) received haplo-HSCT as salvage therapy. It included patients with refractory tumors without remission by the start of haplo-HSCT and patients with early relapses after HLA-matched related or unrelated allo-HSCT. The second group (n = 35) received haplo-HSCT on reaching the optimal pretransplant status (“non-salvage”).

Results. The incidence of cytomegalovirus (CMV) reactivation, invasive mycosis, and bacterial infections was 70.4 %, 11.5 %, and 75.4 %, respectively. CMV reactivation and invasive mycosis did not affect either the 35- or the 100-day overall survival (OS). For the first time bacterial infections were stratified based on severity according to Sepsis 3 consensus, which allowed to identify groups of patients with unfavorable prognosis. Severe bacterial infections (sepsis and septic shock) correlated with worse early and long-term results, especially in patients without remission by the start of haplo-HSCT, whereas febrile neutropenia/bloodstream infection did not affect OS. On the whole, mortality associated with bacterial infections was 26.2 %.

Conclusion. The main factor affecting early lethality after haplo-HSCT is a severe bacterial infection. The key risk factor is lack of remission by the start of haplo-HSCT. Sepsis 3 criteria can be applied in the period of postcytostatic cytopenia to identify the group of patients with most unfavorable prognosis (septic shock). The implementation of current infection control methods (genotyping of multiple drug resistant strains and timely determining the strategy of antimicrobial chemotherapy on the basis of the results obtained) into everyday clinical practice can improve the treatment outcomes in this category of patients.

Keywords: haploidentical hematopoietic stem cells transplantation, infectious complications, sepsis, septic shock, cytomegalovirus reactivation, invasive mycosis.

Received: April 11, 2019

Accepted: September 18, 2019

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Infectious Complications in Multiple Myeloma Patients Receiving Various Antitumor Regimens

AA Novikova, GA Klyasova, EO Gribanova, VV Ryzhko, TA Tupoleva, LP Mendeleeva, VG Savchenko

National Medical Hematology Research Center, 4a Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

For correspondence: Anna Aleksandrovna Novikova, 4a Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(916)873-15-72; e-mail: annanovikova11@mail.ru

For citation: Novikova AA, Klyasova GA, Gribanova EO, et al. Infectious Complications in Multiple Myeloma Patients Receiving Various Antitumor Regimens. Clinical oncohematology. 2019;12(2):231–9.

DOI: 10.21320/2500-2139-2019-12-2-231-239


ABSTRACT

Aim. To study infectious complications and factors attributable to them as reported in multiple myeloma (MM) patients in the framework of state-of-the-art anticancer therapy.

Materials & Methods. The study included MM patients who received regimens based on bortezomib, lenalidomide, and bendamustine from January 2013 to August 2018. The regimens including thalidomide, melphalan, and aggressive antitumor treatment constituted the group of “others”.

Results. The study enrolled 174 patients (82 men and 92 women with median age of 61 years) with newly diagnosed MM (with median follow-up of 5.6 months). A total of 1362 courses of antitumor treatment were administered: 895 bortezomib (n = 174), 306 lenalidomide (n = 68), and 63 bendamustine (n = 22) regimens. The category of “others” included 98 treatment courses (n = 34). Infectious complications were reported in 129 (74.1 %) MM patients throughout the period of 344 (25.3 %) courses of antitumor treatment. Infection incidence on bortezomib (24.4 %), lenalidomide (20.3 %), and bendamustine (27 %) therapies was similar, and fell clearly below the infection incidence registered on the regimens constituting the group of “others” (48 %; р < 0.01). The most common infectious complications were pneumonias (54.9 %), urinary (24.7 %), and herpesviral infections (22.9 %). Herpesviral infections were predominantly associated with bortezomib treatment (29.8 %; p < 0.05). Significant factors (р < 0.05) associated with infection development were leukopenia, the presence of central venous catheter (CVC), need for blood transfusion, MM progression or relapse.

Conclusion. Infection incidence in MM patients receiving bortezomib, lenalidomide, and bendamustine anticancer therapy appeared to be similar, but considerably lower than in patients who received antitumor regimens belonging to category “others”. The prevalent type of infectious complications was pneumonia. Herpesviral infections were most common on bortezomib regimens. Factors related to infection development throughout all therapies were leukopenia, the presence of CVC, need for blood transfusion, MM progression or relapse.

Keywords: multiple myeloma, infectious complications, risk factors.

Received: January 26, 2019

Accepted: March 29, 2019

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Diagnostic Value of C-Reactive Protein as Marker of Infections in Patients with De Novo Acute Myeloid Leukemias

L.N. Tarasova1, S.G. Vladimirova1, V.V. Cherepanova2

1 Kirov Scientific Research Institute for Hematology and Blood Transfusion under the Federal Medico-Biological Agency of Russia, 72 Krasnoarmeiskaya str., Kirov, Russian Federation, 610027

2 Municipal Hospital No. 33, 54 pr-t Lenina, Nizhny Novgorod, Russian Federation, 603122

For correspondence: Lyudmila Nikolaevna Tarasova, DSci, Professor, 72 Krasnoarmeiskaya str., Kirov, Russian Federation, 610027; Tel.: +7(8332)67-57-00; e-mail: vlsg@mail.ru

For citation: Tarasova LN, Vladimirova SG, Cherepanova VV. Diagnostic Value of C-Reactive Protein as Marker of Infections in Patients with De Novo Acute Myeloid Leukemias. Clinical oncohematology. 2015;8(4):442–446 (In Russ).

DOI: 10.21320/2500-2139-2015-8-4-442-446


ABSTRACT

Aim. To determine diagnostically relevant C-protein levels (CRP) as an early infection marker in patients with de novo acute myeloid leukemias (AML), to evaluate the dependence of CRP concentrations on the WBC count and leukemic blast cells in the peripheral blood.

Methods. CRP was tested in 39 patients with de novo AML (17 males and 22 females) at the age of 20 to 76 years (median age is 49). AML types according to the FAB grading were as follows: М0 — 2, М1 — 4, М2 — 23, М4 — 8, and М5 — 2 patients.

Results. CRP concentrations in patients without symptoms of an infection (n = 16) were within the range from 0 to 43 mg/l (median 5.5 mg/l). The Spearman’s rank correlation coefficients between the CRP level and WBC and blast cell counts were 0.664 (= 0.006) and 0.473 (= 0.062), respectively. The obtained data confirm activation of CRP synthesis in case of leukemia. In patients with an infection and/or fever (n = 23), CRP levels were significantly higher than those in patients without an infection: 8–383 mg/l (median 81 mg/l). No correlation between the CRP level and WBC and blast cell counts was found. Therefore, the CRP synthesis during the onset of AML is significantly increased as a response to the infection. In groups of patients with and without infections, 95% CI were equal to 0–40 mg/l and 12–315 mg/l, respectively. Since they overlap within the range from 12 to 40 mg/l, they may be considered a «grey zone». The CRP concentrations within this range suggest infection. CRP levels lower than 12 mg/l or higher than 40 mg/l with a high degree of probability confirm either absence or presence of infectious complications, respectively.

Conclusion. Therefore, CRP is an accessible and informative marker of infection in patients with AML during the onset of the disease. Monitoring of its levels permits to start a timely antimicrobial therapy; at that, the efficacy of the therapy can be assessed based on the dynamics of this parameter.


Keywords: acute myeloid leukemias, infectious complications, acute-phase proteins, C-reactive protein, blast cells, white blood cells.

Received: April 20, 2015

Accepted: October 22, 2015

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