Patients with Acute Myelogenous Leukemia (AML) or High-Risk Myelodysplastic Syndrome (HR-MDS) Treated with Targeted Therapy May Benefit from Prophylactic Measures Against Infections.
Authors: Mattiuzzi Gloria N. , Cortes Jorge E. , Faderl Stefan , Cabanillas Maria E. , Giles Francis J. , O’Brien Susan , Garcia-Manero Guillermo , Kantarjian Hagop H. 
Published: April 2020

Targeted therapy (TT) has emerged as an alternative for patients (pts) 60 years or older with hematologic malignancies. It has been suggested that these approaches produce fewer and less severe side effects than conventional chemotherapy (CC) and could potentially decrease mortality. In the current study, pts with AML or HR-MDS treated with TT and CC were compared with regard to infectious complications and induction mortality. Supportive care measures for pts on CC were given according to our departmental guidelines (protective environment (PE) was offered and antibacterial, antifungal and antiviral prophylaxis were given from D1 to ANC ≥ 500). Pts on TT were given supportive care measures according to protocol requirements. HR-MDS pts: 29 pts were treated with TT and 13 with CC. Pts on TT were significantly older than those on CC (median age: 66(r: 46–85) and 59(r: 17–73) respectively, p=0.02). All 42 pts (TT and CC) had Zubrod performance status (PS) ≤ 2. 16/29 (90%) pts on TT received Decitabine; 2 pts received 5-AZA containing regimens and 1 pt received rosiglitazone + targetrin. Nine pts (69%) on CC had high-dose ara-C (HDAC) containing regimens; 1 pt received cloretazine + hydrea and 3 pts had low-dose ara-C (LDAC) + clofarabine. AML pts: 43 pts were treated with TT and 282 received CC. Pts on TT were significantly older than those on CC (median age: 75(r: 39–86) and 62(r: 17–84) respectively, p&lt;0.001). The majority of the pts in TT (91%) and CC (97%) had PS ≤ 2. Decitabine was given to 40% (17/43) of pts on TT, 25% received 5-AZA containing regimens, 35% had others. HDAC containing regimens were given to 60% of pts on CC and clofarabine and/or LDAC to 40%. Table 1 and 2 show outcome and infectious episodes (IE) in pts with MDS and AML, respectively. Conclusions: Although pts with AML or HR-MDS treated with TT develop significantly fewer number of IE compared to pts treated with CC the severity of such infections lead to similar mortality rate than pts treated with CC. Pts treated with TT may benefit from prophylactic measures against infections.

Table 1 Outcome in MDS TT (N=29) CC (N=13) 12 aspergillosis, 1 MRSA sepsis; 2p=ns Response, n(%) Overall response 18(62) 8(61) Resistant 8(28) 4(31) Induction death 3(10) 1(8) p=0.787 Cause of Death, n(%) Infections 3(100)1 - Progressive disease - 1(100) Pts on prophylaxis, n(%) Fungal 11(38) 12(92) p=0.001 Bacterial 19(66) 9(69) p=0.810 Pts in PE, n(%) 0 10(77) p&lt;0.001 Pts with IE, n(%) 15(52) 11(85) p=0.042 IE2, n(%) 19 14 Bacterial 5(26) 2(14) FUO 8(42) 9(64) Pneumonia unknown origin 2(11) 3(21) Fungal 2(11) 0 Others 2(11) 0 Table 2 Outcome in AML TT (N=43) CC(N=282) 1TT:sepsis=5, CC:fungal=4, sepsis=16; 2multiorgan failure; 3p=ns Response, n(%) Overall response 12(28) 180(64) Resistant 27(58) 67(24) Induction death 6(14) 35(12) p=0.779 Cause of death, n(%) Infection1 5(83) 20(57) MOF2 1(14) 7(20) Others - 8(23) Pts on prophylaxis, n(%) Fungal 16(37) 260(92) p=0.001 Bacterial 24(56) 282(100) p=0.001 Pts in PE, n(%) 6(14) 214(76) p&lt;0.001 Pts with IE, n(%) 22(51) 247(88) p&lt;0.001 IE3, n(%) 31 405 Bacterial 7(22) 88(22) FUO 13(42) 202(50) Pneumonia unknown origin 6(19) 93(23) Fungal 1(3) 10(2) Virus 2(6) 6(1) Others 2(6) 6(1)