**6. Infections related to HSCT in MM**

Prior to the era of novel therapies for MM, studies in patients with HMs receiving autologous HSCT showed that there was no significant difference in incidence, type of infection, and clinical course of infection between patients with MM and patients with other HMs [134, 135]. However, a recent study showed that in-hospital mortality in patients with MM receiving autologous HSCT was approximately 1.5% and that there was no significant difference in mortality between elderly individuals and young patients [136]. Nevertheless, elderly patients were more likely to develop complications such as pneumonia, septic shock, acute respiratory failure needing endotracheal intubation, acute renal failure, and cardiac arrhythmias [136].

In patients with MM having dialysis-dependent renal failure are at higher risk of FN and infectious complications such as septic shock compared to patients without renal failure [137]. Patients with MM subjected to autologous HSCT are at higher risk of developing bacterial meningitis, which is associated with high rates of mortality and morbidity [138]. MM patients having MBL2 (mannan-binding lectin, which is part of the innate immune system that protects against severe infections during autologous HSCT) polymorphism are at risk of severe infections particularly after receiving HD-melphalan and autologous HSCT [139]. In addition to the administration of prophylactic antimicrobials in patients with HR-MM and in recipients of HSCT, strategies to reduce the incidence of infectious complications include administration of IV immunoglobulins and vaccination despite the likelihood of vaccination failure [140, 141].

During stem cell mobilization, infections related to central venous catheters are likely to occur with predominance of GPB [142]. Conditioning therapy with HD-melphalan causes mucositis and myelosuppression with neutropenia [14]. The use of melphalan is associated with colitis, pneumonia, and bacteremia, and these infections are usually caused by the following encapsulated bacteria, *Candida* species and *Aspergillus* species [14].

During the post-transplant period, organisms such as *Clostridium difficile*, CMV, HSV, VZV, PJP, and other opportunistic organisms dominate [13, 14, 141]. The sites of infection during this period are gastrointestinal, respiratory, and urinary tracts [13, 14]. In the pre-engraftment period of time: bacteremia, pneumonia, cellulitis, and gastrointestinal infections with *Clostridium difficile* occur, while VZV, CMV, *Clostridium difficile*, and PJP with gastrointestinal tract, lung and skin infections dominate in the post-engraftment period of time [14]. Bacteremia in recipients of autologous HSCT is associated with previous bortezomib therapy and elevated beta-2 microglobulin level [141]. Recently, a significant increase in the incidence of infections caused by multidrug resistant organisms (MDROs) has been encountered [143]. Also, colonization with MDROs in recipients of autologous HSCT has negative impact on OS due to the profound immunosuppression caused by the HMs and their treatments [143].

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Reactivation of HBV is a well-recognized complication in patients with chronic HBV infection undergoing cytotoxic chemotherapy or immunosuppressive treatment [144]. In patients undergoing autologous HSCT, reverse seroconversion of HBV is not a rare complication and this poses concerns about possible complications in such severely immunocompromised individuals [144]. There is an extremely low incidence of PJP in recipients of autologous HSCT; thus, routine PJP prophylaxis should not be offered routinely to this population group. However, patients who require systemic corticosteroid therapy in the post-transplant period are candidates for PJP prophylaxis [145].
