Acute Myelogenous Leukemia Supportive Care in Pediatric Oncology irantextbook.ir 93df

206 × 10 9 L vs. 116 × 10 9 L. Metabolic complica- tions were uncommon although more prevalent in those with FAB M4M5 subtypes. Twelve of the 17 deaths occurred due to hemorrhage gastroin- testinal, pulmonary or intracranial. Earlier studies have reported a much higher death rate, likely due in part to less intensive supportive care measures Wald et al. 1982 ; Bunin and Pui 1985 ; Creutzig et al. 2004 ; Inaba et al. 2008 . Although signifi cant data are lack- ing, one study in adult AML M5 patients with HL and pulmonary symptoms has shown poten- tial benefi t with the addition of dexamethasone to improve lung function in the acute period Azoulay et al. 2012 . The utilization of leuka- pheresis in AML is controversial and discussed further in Sect. 6.7 .

6.4 Acute Promyelocytic Leukemia

HL is an uncommon presenting feature in APL although pediatric patients have an increased incidence of microgranular APL M3v with concomitant HL Rovelli et al. 1992 ; Guglielmi et al. 1998 ; de Botton et al. 2004 . HL can more commonly be seen as part of APL differentia- tion syndrome previously called retinoic acid syndrome after commencement of either all- trans retinoic acid ATRA or arsenic trioxide ATO therapy Vahdat et al. 1994 ; Camacho et al. 2000 ; Levy et al. 2008 ; Zhang et al. 2008 ; Sanz et al. 2009 ; Zhou et al. 2010 . In some studies, increasing leukocytosis WBC 10 × 10 9 L was a risk factor for the develop- ment of the clinical fi ndings of APL differentia- tion syndrome such as unexplained fever, weight gain, respiratory distress, pulmonary infi ltrates, pleural effusions or pericarditis Frankel et al. 1992 ; Vahdat et al. 1994 ; Camacho et al. 2000 . HL either at diagnosis or after initiation of dif- ferentiating therapy is a risk factor for early death, especially from ICH secondary to dis- seminated intravascular coagulation DIC Rovelli et al. 1992 ; Roberts et al. 2000 ; Zhang et al. 2008 ; Zhou et al. 2010 . Due to the risk of early death from DIC and hemorrhage, especially in those with the highest WBC counts, it is vital to initiate supportive care and induction therapy with ATRA andor ATO emergently Sanz et al. 2005 , 2009 ; Tallman and Altman 2009 . In lieu of random- ized data, expert guidelines recommend treat- ment of coagulopathy with fresh frozen plasma, fi brinogen fi brinogen concentrate or cryopre- cipitate, and platelet transfusion to maintain fi brinogen 150 mgdL and platelets 50 × 10 9 L at the minimum in those with HL, with frequent i.e., every 6–8 h monitoring and correction Sanz et al. 2005 , 2009 ; Tallman and Altman 2009 . Studies on the complementary use of antifi brinolytics such as tranexamic acid have not shown benefi t Sanz et al. 2009 . Diagnostic lumbar puncture and placement of a central venous catheter should be avoided until the coagulopathy has resolved Sanz et al. 2005 , 2009 ; Tallman and Altman 2009 . Initiation of treatment with a differentiating agent should start prior to genetic confi rmation of diagnosis in those cases with suffi cient clinical suspicion Sanz et al. 2005 , 2009 ; Tallman and Altman 2009 . The clinician should be cognizant of the risk for HL development and concomitant DIC after initiation of either ATRA or ATO. In the pediatric North American INT0129 APL trial, hydroxyurea was initiated at a dose of 1 gm 2 and ATRA held if the WBC rose to 30 × 10 9 L during ATRA therapy until the WBC count was 10 × 10 9 L Gregory et al. 2009 . In a Chinese study of 19 children with APL who received single-agent ATO, all developed an increase in WBC count with induction ATO with 5 having WBC 100 × 10 9 L Zhou et al. 2010 . The two children with the highest WBC counts, 178 × 10 9 L and 252 × 10 9 L after ATO initiation, both died from ICH. Zhou et al. 2010 initiated hydroxyurea for all WBC 20 × 10 9 L while also decreasing the ATO dose or even holding it in patients with severe leukocytosis. The benefi t of holding ATO therapy with HL is unclear Levy et al. 2008 ; Sanz et al. 2009 . Oral corticoste- roids, which are utilized as treatment for APL differentiation syndrome, have also been sug- gested as a prophylactic agent with WBC 5–50 × 10 9 L or with the initiation of induction therapy in all patients to prevent the development of subsequent HL as well as severe pulmonary or CNS symptoms Wiley and Firkin 1995 ; Sanz et al. 2005 , 2009 ; Tallman and Altman 2009 Randomized data are lacking. The use of leuka- pheresis in APL with HL is controversial and dis- cussed in Sect. 6.7 .

6.5 Chronic Myelogenous

Leukemia HL is reported to be more common in pediatric patients with CML as compared to adults Rowe and Lichtman 1984 ; Millot et al. 2005 . Even with the high WBC counts at presentation, preva- lence of leukostasis secondary to pediatric CML is thought to be uncommon although it was seen frequently in the small review by Rowe and Lichtman 1984 . Symptoms of leukostasis in CML patients can include neurologic complaints such as papilledema, cranial nerve defects, and tinnitus, respiratory complaints, and priapism Rowe and Lichtman 1984 . Priapism has been noted in pediatric ALL and CML Castagnetti et al. 2008 ; Vaitkevičienė et al. 2013 . Management of HL in CML prior to the initiation of tyrosine kinase inhibitor therapy can be accomplished with hydroxyurea Schwartz and Canellos 1975 . Management of pediatric patients with signs and symptoms of leukostasis lacks an evidence basis in the literature although sources recommend utilization of chemotherapy in addition to leukapheresis Rowe and Lichtman 1984 ; Castagnetti et al. 2008 . For low-fl ow ischemic priapism in particular, adult guide- lines recommend chemotherapy, leukapheresis, and urologic therapy with therapeutic aspiration and intracavernous sympathomimetics if aspira- tion alone is not successful Montague et al. 2003 ; Rogers et al. 2012 . Castagnetti et al. 2008 suggest patients can be managed without invasive urologic procedures utilizing chemo- therapy and leukapheresis alone; however, their small cohort required a long period of time to recover from priapism and half did not receive leukapheresis. In addition they recommend the use of anticoagulation with low-molecular- weight heparin especially with concomitant thrombocytosis although signifi cant evidence on utility is lacking. On long-term follow-up, none of their patient cohort had developed clinical evi- dence of erectile dysfunction.

6.6 Management of Tumor

Lysis Syndrome The general management of tumor lysis syn- drome TLS is discussed in Chap. 3 . Patients with HL are at increased risk of both laboratory and clinical TLS, especially those with ALL. Truong et al. 2007 showed that WBC 20 × 10 9 L was an independent risk factor for the development of TLS in pediatric ALL. Montesinos et al. 2008 similarly reported that WBC 25 × 10 9 L was an independent risk factor for TLS in adult AML patients, but it is unclear if TLS is a signifi cant issue in pediatric AML even with HL Inaba et al. 2008 ; Sung et al. 2012 . Prevention through the utilization of hyperhydra- tion, urine alkalinization, and allopurinol are all proven methods to reduce the risk of metabolic complications in pediatric patients with HL and ALL Maurer et al. 1988 ; Lascari 1991 . Maurer et al. 1988 showed no benefi t in preventing metabolic derangement through the use of low- dose prednisone prior to initiation of induction chemotherapy in pediatric ALL patients with WBC 200 × 10 9 L. The most recent expert TLS guidelines list both ALL and AML with concomitant HL as high-risk for the development of TLS and recom- mend prophylactic use of rasburicase in addition to aggressive hydration to prevent hyperuricemia Cairo et al. 2010 . These recommendations con- curred with the Italian consensus guidelines for ALL, although in the Italian opinion TLS was rare in AML even with HL and therefore should not be considered high-risk Tosi et al. 2008 . Cairo et al. 2010 recommend one dose of rasburicase at a dose of 0.1–0.2 mgkg prior to the initiation of therapy, while Tosi et al. 2008 recommend con- tinuing daily therapy at a dose of 0.2 mgkgday for 3–5 days. Additionally, the concomitant use of allopurinol due to the very rarely reported pre- cipitation of uric acid precursor xanthine and