The preliminary search strategy retrieved 630 pertinent studies. Following screening the titles and abstracts, 206 articles were selected for the final evaluation. This systematic review included 28 studies that met our inclusion criteria. Studies showing the combined cost of chemotherapy (induction + consolidation) [9] and cost estimated through modeling [21,22,23] were excluded. The comprehensive search strategy is shown in Fig. 1. Table 1 represents the extracted data from the included studies.

Screening strategy for the systematic review in accordance with PRISMA guidelines

The characteristics of per-patient cost studies included in this review are summarized in Table 2. Nine studies were conducted in France [24,25,26,27,28,29,30,31,32], six in the Netherlands [33,34,35,36,37,38] and Spain [39,40,41,42,43,44], three in Sweden [45,46,47], two in Germany [48, 49], and one each from Italy and Austria. In 25 studies, the costs were recorded in Euros (€), whereas the costs were reported in US dollars (US$) in two studies [34, 40], and Deutsche Mark (DEM) [49] in single studies. Twenty-two of these studies relied on retrospective data extracted from patient medical records, while the remaining six utilized prospective data. For cost calculation, 13 research studies employed a bottom-up approach, whereas 11 studies employed a top-down approach. Two studies employed both the bottom-up approach and the top-down approach. In the included studies, the number of AML patients ranged from 12 to 39,568. There was no missing data across the included studies and each study provided a complete dataset.

The costs of induction treatment are shown in Table 3. The cost components of induction chemotherapy include inpatient hospitalization, consultation, diagnosis, blood products, chemotherapy, and other medications. The mean per-patient cost of the induction phase of chemotherapy in the European Union is €59,646. The total cost of induction was estimated in Spain, France, Netherlands, Germany, and Italy as €92,378 [39, 43], €77,844 [25, 32], €61,643 [33, 34], €46,113 [49], and €20,254 [50], respectively. Patient hospitalization costs for induction therapy were reported in Spain and the Netherlands as €72,757 [39, 43], and €32,964 [33], respectively. Consultation costs have been reported in Spain and the Netherlands as €9227 [39], and €622 [33], respectively. In addition, the medication cost, blood product cost, and diagnosis cost were reported in the Netherlands as €8147, €8664, and €9403, respectively [33]. Inpatient hospitalization was the major cost driver in Spain and the Netherlands, followed by diagnostic costs in the Netherlands and consultation costs in Spain.

The consolidation costs are listed in Table 4. Compared with studies that estimated induction therapy costs, minimal data is available on the cost of consolidation therapy. It is less expensive than induction therapy. The cost components of consolidation chemotherapy include inpatient hospitalization, consultation, diagnosis, blood products, chemotherapy, and other medications. The mean per-patient cost of the consolidation phase of chemotherapy in the European Union was €37,178. The mean total cost of consolidation was estimated in the Netherlands and Germany as €42,137 [33, 34], and €32,220 [48, 49], respectively. Inpatient hospitalization costs were reported in the Netherlands and Germany as €28,488 [33] and €31,343 [48], respectively. Consultation cost was reported in the Netherlands and Germany as €1980 [33] and €150 [48], respectively. The cost of medications was reported only in the Netherlands as €4544 [33]. The cost of blood products was reported in the Netherlands, France, and Germany as €5159 [33], €6122 [24, 26], and €1790 [48], respectively. Lastly, the diagnostic costs were reported in the Netherlands and Germany as €5715 [33] and €53 [48], respectively. The cost of blood products stood third after the cost of diagnosis and hospitalization in the Netherlands and stood second to the cost of hospitalization during consolidation therapy in Germany.

Transplantation costs are listed in Table 5. The components of the cost of transplantation include inpatient hospitalization, consultation, diagnosis, blood products, chemotherapy, and other medications. The mean per-patient cost of transplantation in the European Union was €136,832. The total cost of the transplant was estimated in Sweden, Austria, France, Netherlands, and Spain as €192,628 [46, 47], €188,453 [51], €132,352 [26,27,28,29,30,31], €122,760 [33,34,35,36,37,38], and €47,968 [39,40,41,42, 44], respectively. Patient hospitalization costs during transplantation were reported in Sweden, Austria, France, Spain, and the Netherlands as €173,073 [47], €90,710 [51], €103,640 [28, 29], €63,721 [39, 40]. and €26,868 [33, 35,36,37], respectively. Consultation costs were reported in Spain, Sweden, Austria, France, and the Netherlands as €29,515 [39], €22,467 [47], €1482 [51], €13,769 [29], and €1029 [33, 35,36,37], respectively. The medication cost was reported in Austria, France, Netherlands, and Spain as €30,708 [51], €13,660 [28], €6295 [33, 35,36,37], and €2910 [40], respectively. The cost of blood products was reported in Austria, Sweden, France, Netherlands, and Spain as €22,048 [51], €15,514 [45], €4375 [26, 28], €4373 [33, 35,36,37], and €1372 [40], respectively. In addition, diagnosis costs were reported in Austria, Netherlands, and Spain as €43,503 [51], €6875 [33, 35,36,37], and €394 [40], respectively. Inpatient hospitalization was the primary driver of the transplantation cost followed by diagnostic and medication costs in Austria and consultation costs in Spain and Sweden. A cost comparison of different phases of AML management among European Union countries is shown in Fig. 2.

Cost comparison of different phases of management of acute myeloid leukemia in European Union countries

The included studies showed a score range of 9–12 on the modified Allison Larg scale. Notably, 12 studies demonstrated excellent quality, scoring between 11 and 12, indicating a low risk of bias. The remaining 16 studies displayed a moderate risk of bias, with a quality score range of 9–10. The detailed results of the modified Allison Larg scale are presented in Table 6.