ALL

Antibiotic Treatment of Febrile Neutropenia in Patients with Acute Leukemia

ANTINEOPLASTIC THERAPY COMPLICATIONS , , , , , ,

VA Okhmat, GA Klyasova, EN Parovichnikova, VV Troitskaya, EO Gribanova, VG Savchenko

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

For correspondence: Vladimir Aleksandrovich Okhmat, PhD, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(495)614-92-72; e-mail: okhmatvladimir@mail.ru

For citation: Okhmat VA, Klyasova GA, Parovichnikova EN, et al. Antibiotic Treatment of Febrile Neutropenia in Patients with Acute Leukemia. Clinical oncohematology. 2018;11(1):100-9.

DOI: 10.21320/2500-2139-2018-11-1-100-109

ABSTRACT

Aim. To estimate the efficacy of antibiotic treatment of febrile neutropenia in patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL).

Materials & Methods. The prospective study (2013 to 2015) included 66 AML and 44 ALL patients receiving 480 chemotherapy cycles within the period of 6 months.

Results. Febrile neutropenia was registered during 242 (50 %) chemotherapy cycles occurring more frequently in AML than in ALL patients (93 % vs. 18 %, p < 0.0001). In AML patients infections were more common during induction and consolidation (98 and 89 %) phases compared to ALL patients who most commonly had infection during induction phase (55 %). Compared to ALL patients, AML patients had lower recovery rates after first-line antibiotic monotherapy (24 % vs. 57 %, p < 0.0001), compared to combination therapy (37 % vs. 18 %, p = 0.01). The use of beta-lactam antibiotics in ALL patients was associated with lower recovery rates during the induction phase compared to consolidation phase (47 % vs. 72 %, p = 0.0004). In cases of granulocytopaenia longer that 14 days the clinical recovery rate with administration of the first-line antibiotics and carbapenems accounted for 23–24 % compared to 47 % with other antimicrobials, more commonly with antifungal (21 %) administration. In patients with fever of unknown origin the monotherapy with first-line antibiotics proved to be successful (45 %). In patients with clinically and microbiologically defined infections the best results were achieved by the combined treatment with the beta-lactam antibiotics and other drugs (43 %).

Conclusion. Antibiotic escalation has proved to be the optimal strategy in treatment of ALL patients and in cases of fever of unknown origin. The efficacy of the beta-lactam antibiotic monotherapy was lower in AML patients during the induction phase as well as in cases of continuous neutropenia (> 14 days) and clinically and microbiologically diagnosed infections. The adding of other antimicrobial administration resulted in the recovery in 37–48 % of cases.

Keywords: acute leukemia, AML, ALL, febrile neutropenia, fever of unknown origin, clinically and microbiologically defined infections, antibiotics.

Received: July 2, 2017

Accepted: October 20, 2017

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Allogeneic Hematopoietic Stem Cell Transplantation for ALL Patients with t(12;21)(p13;q22) Translocation

BONE MARROW TRANSPLANTATION , , , ,

N.N. Mamaev1, E.V. Semenova1, N.V. Stancheva1, V.A. Katerina1, I.M. Barkhatov1, A.V. Evdokimov1, E.G. Boychenko2, T.L. Gindina1, V.M. Kravtsova1, L.S. Zubarovskaya1, B.V. Afanasyev1

1 R.M. Gorbacheva Memorial Institute of Children Oncology, Hematology and Transplantation under I.P. Pavlov State Medical University, Saint Petersburg, Russian Federation

2 1st Municipal Children’s Hospital, Saint Petersburg, Russian Federation

For citation: Mamaev N.N., Semenova E.V., Stancheva N.V., Katerina V.A., Barkhatov I.M., Evdokimov A.V., Boichenko E.G., Gindina T.L., Kravtsova V.M., Zubarovskaya L.S., Afanas’ev B.V. Allogeneic Hematopoietic Stem Cell Transplantation for ALL Patients with t(12;21)(p13;q22) Translocation. Klin. onkogematol. 2014; 7(3): 327–34 (In Russ.).

ABSTRACT

The results of allogeneic hematopoietic stem cell transplantation (alloHSCT) in 10 pediatric patients (4 boys, 6 girls at the age of 4 to 17 years, mean age is 9.8 years) with relapses of acute lymphoblastic leukemia (ALL) with TEL-AMLI fusion gene are presented. The first remission duration ranged from 20 to 70 months (mean duration 39.9 months). Transplantation was performed in 6 patients during the second (and further) remission, whereas 4 patients underwent transplantation during the relapse. Six patients received a graft from matched related (n = 3) or unrelated (n = 3) donors, haploidentical HSCT was performed in four other patients because there was no donor. Conditioning regimens were myeloablative in 8 cases and RIC (Reduced Intensity Conditioning) in 2 cases. Successful engrafting took place in 9 (90 %) of 10 patients. Additional haploidentical transplantation was performed in 1 case, when the transplant was rejected.

Monitoring of treatment was performed by means of serial testing of TEL-AMLI fusion gene expression level, of serial donor chimerism and the blast cell count in bone marrow and peripheral blood. The study demonstrated that four patients younger than 4 years had TEL-AML1 gene expression at all stages of their disease, including pre- and post-transplantation period. Due to it, even the donor chimerism and blast cell count in bone marrow and/or peripheral blood changed. On the contrary, in 3 more patients, TEL-AML1 gene expression levels were low before alloHSCT, being absent after HSCT.

In general, seven patients have been monitored for 178–2627 days (at the average of 870 days) including two patients with post-transplant relapses. At the same time, 3 patients died on days 20–263 after transplantation.

The observed difference in response to chemotherapy might be supposedly explained by involvement of not only hematopoietic, but also mesenchymal cells into the leukemic process (this fact was demonstrated for this group of patients by S. Shalapour et al., 2010). But this fact should be confirmed in further studies.

Keywords: ALL, t(12;21)(p13;q22) translocation, alloHSCT, molecular monitoring, difference in response to treatment.

Address correspondence to: nikmamaev524@gmail.com

Accepted: May 22, 2014

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