Discussion:
Based on studies and guidelines, lymphoproliferative disorders, acute
and chronic lymphocytic leukemia and multiple myeloma constitute the
vast majority of PCP cases in hematologic patients and PCP prophylaxis
recommend in them [39,
40]. Based on guidelines, PCP in acute
myeloid leukemia and myelodysplastic syndromes are rare and sparse and
routine prophylaxis in these settings are not recommended. The reason
for this recommendation maybe that PCP as fungi interacts with
lymphocytes and in these myeloid disorders, the main abnormality is in
myeloid precursors [26,
41, 42].
Another explanation is that steroids are used in chemotherapeutic
regimens in lymphoproliferative disorders, lymphocytic leukemia and also
multiple myeloma and this agent beside anti CD20 antibodies have no role
in induction or consolidation therapy in myeloid disorders. The
guidelines up to now recommend prophylaxis for Cytarabine only in
lymphoproliferative disorders [43].
Unlike adults, in pediatric AML, routine prophylaxis for PCP is
recommended [44].
Some studies focuses on the PCP incidence in AML patients. In a study
conducted in Taiwan in 2018, 291 patients with AML were analyzed. 14
patients had definitive PCP and 6 patients had possible PCP. They found
that there was an incidence of 6.8% risk of developing PCP in AML and
2% risk for each cycle of chemotherapy they received and the authors
concluded that, prophylaxis should be considered in AML
[33]. In contrast, Antoine R et al.
in 2015, illustrated about two studies conducted in 1990-1999 and 2014
that among 55 and 321 patients with PCP, only 8 and 9 patients had AML
respectively. The authors concluded that the diagnosis of PCP should not
be part of the initial diagnostic process or therapy in patients with
AML and the prophylaxis is not recommended
[34,
45]. Some sparse case reports infavor
of acute myeloid leukemia and PCP are available. In 2000, the authors
presented a 30 year-old man with AML treated with subcutaneous low dose
cytarabine. After one week he had signs and symptoms of sweet syndrome
and PCP, with bilateral lung infiltration
[37]. Lemez et al. treated 51
patients with AML and 3 patients with Myelodysplastic syndromes with
Daunorubicin and Cytarabine. They received TMP-SMX for prophylaxis of
pneumocystis. Only one of the eighteen patients without TMP-SMX
prophylaxis during the first course of chemotherapy developed PCP that
was treated with intravenous TMP-SMX
[46]. An agent named Gemtuzumab
ozogamicin is an anti CD33 monoclonal antibody which was approved for
treatment of CD33+ AML in induction and consolidation therapy. CD33 is
expressed on monocytes, granulocytes and myeloid progenitors and CD33
targeted therapies lead to myeloid cells depletion
[47]. In results of reported trials
for administering Gemtuzumab in AML patients, there was no increase in
risk of infection due to this agent
[47,
48].
Cytarabine which is the backbone of chemotherapy in myeloid disorders
has an association with increased risk of PCP. Also it has been shown
that T lymphoblasts are more active as compared to myeloblasts in
cellular transport of cytarabine and this suggests that this agent is
not only myelotoxic but is also profoundly immunosuppressive. Despite
recovery of neutropenia, lymphopenia due to prolonged effect of
cytarabine may make the patient susceptible to PCP.
We should also focuses on the role of alveolar macrophages. Macrophages
are the front line of the anti-microbial defenses in the lung alveolar
cavities. The major function of this cell and one of their most
important roles is to fight against organisms and clean them across the
alveolar cavities. Among these agents, Pneumocystis spp.are more sensitive to its killing functions. The most important
biological manifestation of these cells is their ability to regenerate
in this space. This makes them permanently present in this structure, so
called self-renewing system. Given that they have tissue establishment
at the beginning of the embryonic stages called: embryonic prenatal
development. Therefore, they are present in the lungs under any
circumstances. It is one of the cases that despite performing
chemotherapy and bone marrow suppression during the treatment of AML
patients, no serious damage is done to the above function and
capability. Especially in the case of monoclonal antibodies therapies
that, despite their positive effect on myeloid suppression in the bone
marrow, are not able to eliminate alveolar macrophages because they have
very low expression of CD33 surface marker. It can be concluded that in
this malignancy, and during treatment, there is minimal damage to the
function of these cells in killing Pneumocystis spp. and
the need for less prophylactic antibiotic. Further studies can help and
determine the true risk of PCP in patients with AML.