Allogeneic bone marrow transplantation improves the outcome of de novo AML with trilineage dysplasia (AML-TLD)

Abstract

De novo acute myeloid leukemia (AML) with dysplastic features in erythroblasts, granulocytes and megakaryocytes, similar to those in myelodysplastic syndrome (MDS) has been described as AML with trilineage dysplasia (AML-TLD) since 1987. Several reports have suggested that AML-TLD is a subtype of de novo AML in adults and has a poor clinical outcome when treated by conventional chemotherapy. It is not certain whether allogeneic bone marrow transplantation (BMT) brings a favorable outcome for AML-TLD. To evaluate the therapeutic efficacy of allogeneic BMT for AML-TLD, we investigated the clinical data and outcomes of conventional chemotherapy and allogeneic BMT for 118 patients with de novo AML. These patients were registered consecutively for the Japan Adult Leukemia Study Group (JALSG) protocols at our institutes. We treated 28 AML-TLD patients and 90 AML-nonTLD patients with conventional chemotherapeutic protocols. AML-TLD patients did not have a significantly different complete remission (CR) rate (75.0% and 88.4% P = 0.1234), but had a significantly higher relapse rate than AML-nonTLD patients (94.1% and 49.3%, P = 0.0007). The outcome of chemotherapy for AML-TLD was significantly worse than that for AML-nonTLD. The overall survival (OS) and leukemia-free survival (LFS) at 6 years were 9.4% and 0% in AML-TLD group, and 51.9% (P = 0.0017) and 46.3% (P Ͻ 0.0001) in AML-nonTLD group, respectively. Meanwhile, among the patients who underwent allogeneic BMT, five of eight AML-TLD patients and eight of 14 AML-nonTLD patients were alive, and three and five patients survived more than 3 years, respectively. These results suggest that allogeneic BMT can improve the outcome for AML-TLD, which is poor when conventional chemotherapy is given alone. Allogeneic BMT before relapse may be the best therapeutic strategy for AML-TLD patients under 50 years of age if a donor is available.

De novo acute myeloid leukemia with multilineage dysplasia: treatment results and prognostic evaluation from a series of 44 patients treated with fludarabine, cytarabine and G‐CSF (FLAG)

“…Stem cell involvement, frequent occurrence of unfavorable cytogenetics, and advanced age are the main adverse parameters which determine unfavourable clinical outcome in MD-AML patients. The clinico-hematologic characteristics described in our series were substantially similar to those reported in other studies (3)(4)(5)(6)(7). MD-AML was frequently found in FAB M2 and M4 subtypes, while it was not seen in M3.…”

“…The clinico‐hematologic characteristics described in our series were substantially similar to those reported in other studies (3–7). MD‐AML was frequently found in FAB M2 and M4 subtypes, while it was not seen in M3.…”

“…The median number of days for recovery to neutrophils >0.5r10 9 L x1 and platelets >20r10 9 L x1 was 20 and 22, respectively. Patients received a median of nine packed red cells (range 2-18) and 10 platelet units (range [3][4][5][6][7][8][9][10][11][12][13][14][15][16]. Data concerning hematopoietic recovery and supportive therapy are summarized in Table 4.…”

“…Therefore, it remains unclear whether multilineage dysplasia per se or other well recognized adverse prognostic features in AML accounts for the poor clinical outcome reported for patients with MD‐AML. Allogeneic stem cell transplantation (allo‐SCT) can substantially improve the outcome of the disease for patients under 50 yr of age when an HLA‐compatible donor is available (7). However, the majority of MD‐AML cases occur in elderly individuals, so that alternative approaches should be investigated.…”

Acute myeloid leukaemia with myelodysplastic features in children: a report of Japanese Paediatric Leukaemia/Lymphoma Study Group

“…A non-significant difference in RFS was thought to indicate that the difference in EFS was not due to relapse, but mainly to failure to achieve CR. On the other hand, a non-significant difference in OS was probably due to the intensive chemotherapies including high-dose cytarabine and HSCT for patients with induction failures and/or high-risk features, which might temper the negative effect of 'AML-MRC' on survival, as previously reported (Taguchi et al, 2000). In multivariate analysis, morphological dysplasia or myelodysplasia-related cytogenetics failed to show independent prognostic relevance, but FLT3-ITD status solely retained prognostic impact, which agreed with the previous publication in adult patients .…”