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.