Introduction
There are several important issues about patients with immunosuppression
especially patients with malignancy. One of the most important of them
is the higher risk of opportunistic infections which are common among
them especially in patients with hematologic malignancies, who have
received intensified chemotherapeutic regimens
[1, 2].
As we see in literature there are many aspects that may be questionable
during routine clinical practice and some of them would change according
to new findings in clinical guidelines. The major aim of prescribing
prophylactic antimicrobial therapy is to reduce the infection related
morbidity and mortality [3] and the
overwhelming possible infections related complications which may reduce
the treatment tolerability, so use of prophylactic antimicrobials were
introduced from long time ago and that was widely studied
[4, 5].
However these agents are not absolutely without adverse effects.
Pneumocystis jirovecii, is an atypical fungus that transmits via
airborne route in respiratory droplets. This agent is in dormitory state
in immunocompetent hosts, and can transmit to others within sufficiently
close distance [6]. It remains
asymptomatic as long as the host would be immunocompetent
[7]. Once the host becomes
immunocompromised, the organism becomes activated and proliferated
[8].
This agent has several components in its cell wall. The main component
is β-1,3-glucan [9,
10]. The first interaction is between
macrophage receptor dectin-1 and β-1,3-glucan
[11,
12]. This interaction leads to
activation of lung macrophages and then releasing of several
pro-inflammatory cytokines such as Tumor necrosis factor α (TNFα),
Interleukin 8 (IL-8) [13-15]. This
pro-inflammatory state results in neutrophil and other inflammatory
cells recruitment, which is correlated directly to the lung
inflammation, acute respiratory failure
[11,
16]. Patients with malignancy or
immunodeficiency who have impaired in innate immune system function,
cannot clear the fungi and are predispose to Pneumocystis jirovecii
pneumonia (PCP). Also TNF blockade results in lack of immune response to
Pneumocystis [17]. In addition to
innate immunity, lymphocytes especially CD4+ and
CD8+ play a major role in host defense against
pneumocystis jirovecii. TNF, IL-1 and IL-8 directly stimulate T
lymphocyte recruitment and activation
[18,
19].
There are several risk factors that predispose people to developing PCP.
The main factor is impaired cell mediated immunity, which has the
essential role in defending against fungi. When CD4 counts drop below
the 200 cells/mm as in HIV patients, Pneumocystis prophylaxis warranted.
Other causes of predisposition are solid organ transplant especially
renal, heart and lung transplant recipients
[20,
21]. In patients with hematological or
oncological malignancies who receive chemotherapeutic regimens and
become neutropenic, Pneumocystis infection is likely. Also in patients
receiving corticosteroid more than 15-25 mg Prednisolone or more than 4
mg Dexamethasone daily for more than 4 weeks are at higher risk of
developing infection [22,
23]. These amounts of corticosteroid
use are seen in chemotherapeutic regimens especially in lymphoblastic
leukemia or some chemotherapeutic regimens of lymphoma. Higher dose of
corticosteroid (more than 60 mg daily) or concomitant use of
Cyclophosphamide would have an additional risk in developing
Pneumocystis infection [24].
Alemtuzumab that causes T cell depletion predisposes to Pneumocystis
infection. Other chemotherapeutic regimens such as FCR (Fludarabine,
Cyclophosphamide, and Rituximab), ABVD (Adriamycin, Bleomycin,
Vinblastine, and Dacarbazine), R-CHOP (Rituximab, Cyclophosphamide,
Adriamycin, Vincristine, and Prednisolone) in 14 days, also input
patients into higher risk of Pneumocystis infection
[25-28]. The risk of developing
Pneumocystis infection in oncological malignancies are much lower than
in hematological ones, so routine prescription of Pneumocystis
prophylaxis are not recommended. In patients with brain tumors
especially who receive an alkylating agent, Temozolamide as in patients
with high grade gliomas, concurrent use of radiation therapy and also
corticosteroid may increase the risk of infection
[29]. Finally in patients with solid
tumor who receive more than 20 mg Prednisolone or equivalents for more
than four weeks are at increased risk for Pneumocystis infection, so
routine prophylaxis is recommended
[30]. Restoration of CD4 counts with
highly active antiretroviral therapy (HAART) in HIV patients or passing
of nadir phase in patients receiving chemotherapy, leads to decrease the
risk of developing infection [31].
In hematologic malignancies, risk of developing PCP depends strongly on
the underlying disorders. Patients with AML have much lower risk of
Pneumocystis infection and up to now there is no recommendation for
prophylactic use of antimicrobials for Pneumocystis in these patients.
Due to limited information about the PCP incidence in AML patients, this
review assess data on PCP incidence and outcome in AML.