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Decrease in Transfusion Needs in Patients with Higher-Risk Myelodysplastic Syndrome and Acute Myeloid Leukemia Treated with 5-Azacytidine. a Retrospective Study

Panagiotis Theodorou Diamantopoulos, Konstantinos Zervakis, Athanasios G. Galanopoulos, Panagiotis Bakarakos, Vasiliki Papadopoulou, Theodoros Iliakis, Fani Kalala, Nefeli Giannakopoulou, Niki Rougala, Eleni Variami, Aglaia Dimitrakopoulou and Nora-Athina Viniou

Abstract

Introduction

The hypomethylating agent 5-azacytidine (AZA) has been the standard of care for higher risk Myelodysplastic Syndromes (MDS) for the last few years. Its efficacy has been proven in large clinical trials, and its safety has been shown to be superior to that of conventional treatments. We have conducted a retrospective study about the efficacy and safety of 5-azacytidine, as reported and analyzed in our center.

Patients and Methods

Forty four consecutive patients with MDS or Acute Myeloid Leukemia (AML) with 20-30% bone marrow blasts that were treated with AZA during the last 63 months were included in the study. The clinical and laboratory characteristics of the patients were recorded, and the efficacy and safety data were analyzed.

Results

The epidemiologic and hematologic characteristics of the patients are shown in Table 1. The median overall survival was 13 months (1-101) and there was no primary treatment failure (Table 2). Serious adverse events consisted mostly of neutropenic infections (blood stream and pneumonia) (Table 3).

Discussion

Treatment with AZA offered a favorable (complete and partial) response in 34.1% of the patients, and an overall survival of 13 months, with generally predictable toxicities, although hospitalization was frequently inevitable during the first treatment cycles, when supportive treatment was a significant part of the management. A valuable observation is that there was a considerable decrease in the patients’ transfusion needs following treatment (p<0.0001). Our results are consistent with the results of other clinical trials and point out the need for investigational 5-azacytidine combinations.

Male: Female ratio30:14 (2.1 : 1)
Age, Median (Range)73 (54-81)
WHO classification of MDS/AML, N (%)
RAEB-I
RAEB-II
RCMD-RS
RCMD
RARS
CMML
AML
9 (20.5)
18 (40.9)
2 (4.5)
3 (6.7)
1 (2.3)
4 (9.1)
7 (15.9)
IPSS classification, N (%)
Low
Intermediate-1
Intermediate-2
High
Not Applicable (AML)
0 (0)
3 (6.8)
29 (65.9)
5 (11.4)
7 (15.9)
Complete Blood Count Parameters, Median (Range)
Hemoglobin (g/dL)
Absolute Neutrophil Count (x109/L)
Platelet count (x109/L)
8.55 (4.5 - 12.5)
1.08 (0.0 – 16.3)
80.0 (2 – 820)
Transfusion dependence, N (%)39 (88.6)
Transfusions per month, Median (Range)3 (0 – 7)
Table 1.

Epidemiologic and hematologic characteristics.

AZA cycles, Median (Range)5 (1-22)
Actual AZA dose (mg/m2/cycle), Median (Range)75 (59-75)
Actual cycle duration (days), Median (Range)28 (28-40)
Dose reductions due to sustained neutropenia, N (%)6 (13.6)
Temporary AZA interruption, N (%)26 (59.1)
Reason
Sustained cytopenia10/26 (38.5)
Neutropenic Infection15/26 (57.7)
Hemorrhagic Complication1/26 (3.8)
Permanent AZA discontinuation, N (%)23/44 (52.3)
Reason
AML transformation17/23 (73.9)
Recurrent or severe infection4/23 (17.4)
Pyoderma gangrenosum1/23 (4.3)
Allogeneic Bone Marrow Transplantation1/23 (4.3)
AZA cycles till response (according to the IWG criteria), Median (Range)4 (1 – 7)
Response (IWG criteria), N (%)
Complete response
Partial response
Stable disease
Failure
7 (15.9)
8 (18.2)
29 (65.9)
0 (0)
Overall survival (months), Median (Range)13 (1 – 101)
Post treatment transfusion dependence, N (%)34 (77.3)
Transfusions per month (post-treatment), Median (Range)1 (0 – 5)
Death rate, N (%)29/44 (65.9)
Cause of death, N (%)
Infection
Hemorrhage
Cardiac dysrhythmia
24/29 (82.8)
3/29 (10.3)
2/29 (6.9)
Table 2.

Efficacy data

Clinical adverse events, N (%)29/44 (65.9)
Neutropenic Infections26/29 (89.7)
Bloodstream Infection9/26 (34.6)
Lower respiratory infection10/26 (38.5)
Neutropenic Fever8/26 (30.1)
Septic shock2/26 (7.7)
Hemorrhagic events2/29 (6.7)
Cerebral hemorrhage (Grade 5)1/2 (50.0)
Epistaxis (Grade 3)1/2 (50.0)
Other (pyoderma gangrenosum)1/29 (3.4)
Laboratory incidents1, N (%)44/44 (100)
All gradesGrades 3/4
Neutropenia36/44 (81.8)34/44 (77.3)
Anemia44/44 (100)24/44 (54.5)
Thrombocytopenia31/44 (70.5)21/44 (47.7)
Supportive treatment (during AZA administration), N (%)
GCSF administration16/44 (36.4)
Erythropoietin administration7/44 (15.9)
Red blood cell transfusions39/44 (88.6)
Red blood cell transfusions (units/cycle), Median (range)3 (0-7)
Pooled random donor platelet transfusions17 (38.6)
Table 3.

Safety data

1According to the CTCAE Version 4.0

Disclosures No relevant conflicts of interest to declare.

  • * Asterisk with author names denotes non-ASH members.