Title in Chemotherapy for Acute Myeloid Leukemia with High Leukocyte Counts.
Authors: Kyo Taiichi , Imanaka Ryota , Ochi Tetsuro , Okatani Takeshi , Kyo Kohei , Itagaki Mitsuhiro , Nagoshi Hisao , Katayama Yuta , Iwato Koji , Asaoku Hideki 
Published: October 2019

Abstract
Introduction
Chromosomal aberration is a powerful prognostic factor for acute myeloid leukemia (AML). On the other hand, age and high leukocyte counts at diagnosis are additional prognostic factors. In the case of high leukocyte counts, chemotherapy becomes difficult since there is a possibility of developing disseminated intravascular coagulation (DIC) and tumor lysis syndrome (TLS). In our hospital, we conducted leukapheresis for leukemia patients with high leukocyte counts at diagnosis who had not developed DIC, and then we performed the original intensive chemotherapy of our institution (see below). Therefore, we targeted AML patients with leukocyte counts high at diagnosis and analyzed the outcome of the chemotherapy retrospectively.
Patient and methods
We examined AML patients with leukocyte counts of 50000/ul or more who received their first treatment at our institution between April 2009 and December 2013.
We conducted leukapheresis for patients with leukocyte counts of 50000/ul or more who had not developed DIC, followed by our original induction therapy. It consisted of four drugs; idarubicin (IDR) 12mg/m2 (10mg/m2 for 70 years of age or older) days 1, 3, 5, 8 and behenoyl cytosine arabinoside (BH-AC) 350mg/m2 (300mg/m2 for 70 years of age or older) days 1-10, merucaptopurine (6-MP) 70mg/m2 days 1-10, predonisolone (PSL) 20mg/person days 1-6. If the patient had developed DIC, we performed this induction therapy treating the DIC with recombinant human soluble thrombomodulin (rTM) and gabexate mesylsate (FOY). Since the release of rasburicase in April 2010, we used it to prevent TLS. After induction therapy, we performed consolidation therapy, which consisted of mitoxantrone + cytarabine, and then maintenance therapy. This consisted of two courses; BAMP therapy (BH-AC, Aclarcin, 6-MP, PSL) and miniIBMP + VCR therapy (IDR, BHAC, 6- MP, PSL) alternately. We performed hematopoietic stem cell transplantation (HSCT) for patients with relapse during suitable age and other eligible cases.
Result
A total of 33 patients with newly diagnosed AML were examined. There were 16 men and 17 women whose median age was 70 years (range, 17-93 years). The elderly patients over the age of 60 were 21/33 (63.6%). Median follow-time was 24 months (range 2-60 months). Leukocyte counts at the time of diagnosis were 50,400-445,900/ul (median 107,700/ul), 17 patients (15.5%) had counts of over 100,000/ul. Leukapheresis was performed on 7 patients and leukocyte reduction rate was 41.7%-75.4%. Serious complications were not observed during the procedure. Serum lactate dehydrogenase (LDH) value was 283-3645 U/L (median 1111 U/L) and serum uric acid value was 2-13.7 mg/dl (median 6.5 mg/dl). We administered rasbricase to 20/33 (60.6%) patients and three (9.1%) patients developed TLS. Seventeen patients (51.5%) underwent DIC, 9 patients were at diagnosis and the remaining 8 patients were after initiation of the induction therapy. We treated DIC with FOY single agent (5 patients), rTM single agent (4 patients) and combination of rTM and FOY (8 patients) and then all patients showed improvement. Karyotype was as follows: Good risk in 3 (9.1%) patients, two had t(15;17) and one had t(8;21); intermediate risk in 23 patients (69.7%), thirteen had normal karyotype, 3 patients had trisomy 8 and 4 patients had others; poor risk in 7 patients (21.2%), six patients had complex karyotype and one patient had monosomy 7. We performed bone marrow aspiration and examination of cerebrospinal fluid after the induction therapy. Twenty-seven (81.8%) patients achieved complete remission, one (3.0%) patient had partial remission and four (12.1%) patients were refractory. There were 10 (30.3%) patients who had central nerve invasion. One patient died of pulmonary hemorrhage and TLS during the induction therapy. One patient received HSCT during the first CR and the remaining 4 patients did so after relapse. Seventeen (51.5%) patients are alive and the median survival time was 13 months, the 3-year overall survival was 40%.
Conclusion
Intensive chemotherapy was feasible and effective with the supporting therapy if the patient was elderly and had high leukocyte counts.

Disclosures
No relevant conflicts of interest to declare.