Abstract
Introduction
Acute panmyelosis with myelofibrosis (APMF) is classified under acute myeloid leukemia not otherwise specified by World Health organization (WHO). The clinical course of this entity is rapidly progressive and fatal, therefore, it is essential to make the accurate diagnosis and distinguish it from its mimickers, particularly acute megakaryoblastic leukemia; AML-M7 (AMKL). The main objective of this study is to identify clinical and pathologic features which could help distinguish APMF from AMKL.
Methods
We evaluated all patients treated at our institution between 1994 and 2013, with APMF and AMKL. We retrospectively reviewed their clinical data, laboratory results, and initial bone marrow morphologic evaluation. The lineage of blasts was evaluated using immunohistochemical staining with antibodies to CD34, anti-megakaryocyte antibodies CD41, CD61, and polyclonal factor VIII. Flow cytometry and cytogenetic studies were reviewed.
Results
i) Clinical characteristics
28 patients were studied which included 8 with APMF (median age 63 years) and 20 with AMKL (median age 65 years). Splenomegaly was commonly seen in AMKL (40%) as opposed to APMF (12.5%) (P=0.21). None of the APMF patients had an antecedent hematologic malignancy, compared to 50% of AMKL patients (p=0.02). Accordingly, APMF patients had a lower incidence of the JAK2V617F mutation compared to AMKL (14% vs. 78%, p=0.04).
ii) Pathological features
Patients with APMF had a hypercellular marrow with increased erythropoiesis (87% vs. 10%, p<0.01) and granulopoiesis (100% vs. 25%, p<0.01), with lower bone marrow blast percentage (14% vs. 33%, p<0.01), with all blasts staining positive for CD34 (p=0.23) compared with AMKL. In AMKL, the majority of blasts stain positive for anti-megakaryocytic antibodies CD61 (100% vs. 30%, p=0.02), CD41 (75% vs. 20%, p=0.10), and factor VIII (50% vs. 20%, p=0.02). On flow cytometry, all cases of APMF demonstrated multilineage proliferation with subsets of blasts positive for CD61, CD117, and MPO. In comparison, all cases of AMKL expressed megakaryocytic marker CD61.
iii) Treatment
Half of our patients received intensive induction chemotherapy in each group. Median survival was similar in APMF and AMKL of 8.6 and 7.6 months respectively (P=0.82). Of the 8 APMF patients, two are alive, with follow-up duration of 14 and 20 months, respectively. In the AMKL group, only one patient is alive, with follow-up duration of 55 months. All three patients have undergone allogeneic bone marrow transplant.
Conclusion
In summary, our study illustrated important clinical and pathologic differences between APMF and AMKL, two similar but distinct conditions. Allogenic stem cell transplant has shown promise in limited number of cases. Future trials evaluating the efficacy of novel therapies are warranted.
Clinical and Laboratory features including treatment details of patients with APMF and AMKL
| APMF N=8 | AMKL N=20 | P-value | |
| Age in years (median) | 63 | 65 | 0.11 |
| Gender, M:F | 5:3 | 10:10 | 0.69 |
| Splenomegaly at diagnosis, n (%) | 1 (12.5) | 8 (40) | 0.21 |
| Antecedent hematological malignancy | 0 | 8- myeloproliferative neoplasm 2- myelodysplastic syndromes | 0.02 |
| Hgb [median] g/dl | 9.6 | 8.7 | 0.73 |
| WBC [median] x 109/L | 1.1 | 4.4 | 0.15 |
| Platelets [median ] X 109/L | 28 | 36 | 0.29 |
| Blast % [median] | 2 | 13 | 0.47 |
| LDH [median] | 422 | 709 | 0.12 |
| JAK2V617F mutation, n (%) | 1/7 (14) | 7/9 (78) | 0.04 |
| Bone marrow Cellularity, n (%): - Hypercellular - Normocellular - Hypocellular | 8 (100) | 13 (65) 4 (20) 3 (15) | 0.07 0.29 0.54 |
| ↑erythropoiesis, n (%) | 7 (87) | 2 (10) | <0.01 |
| Left shift, n (%) | 5 (62) | 6 (30) | 0.20 |
| ↑granulopoiesis, n (%) | 8 (100) | 5 (25) | <0.01 |
| Left shift, n (%) | 8 (100) | 9 (55) | 0.01 |
| ↑megakaryopoiesis, n (%) | 7 (87) | 16 (80) | 1.00 |
| Micromegakaryocytes, n (%) | 7 (87) | 18 (90) | 1.00 |
| ↓megakaryocyte nuclear lobulation, n(%) | 7 (87) | 12 (60) | 0.21 |
| Clustering of megakaryocytes, n (%) | 5 (62) | 13 (65) | 1.00 |
| BM blast % [median] | 33 | 14 | <0.01 |
| % of blasts CD34 + [median] | 100 | 30 | 0.23 |
| % of blasts + for megakaryocyte markers [median] - CD61+ - CD41+ - Factor VIII+ | 30 20 20 | 100 75 50 | 0.02 0.10 0.01 |
| Reticulin fibrosis ≥ 3+, n (%) | 5 (62) | 9 (45) | 0.67 |
| Complex karyotype, n (%) | 4(50) | 10(50) | 1.00 |
| Treatment, n (%) - Induction chemotherapy - Hypomethylating agent - Clinical trial - Supportive care | 4 (50) 0 0 4(50) | 10(50) 2(10) 2 (10) 6(30) | |
| Allogeneic bone marrow transplant, n (%) | 3 (38) | 3 (15) | |
| Overall survival in months (median) | 8.67 | 7.61 | 0.82 |
| APMF N=8 | AMKL N=20 | P-value | |
| Age in years (median) | 63 | 65 | 0.11 |
| Gender, M:F | 5:3 | 10:10 | 0.69 |
| Splenomegaly at diagnosis, n (%) | 1 (12.5) | 8 (40) | 0.21 |
| Antecedent hematological malignancy | 0 | 8- myeloproliferative neoplasm 2- myelodysplastic syndromes | 0.02 |
| Hgb [median] g/dl | 9.6 | 8.7 | 0.73 |
| WBC [median] x 109/L | 1.1 | 4.4 | 0.15 |
| Platelets [median ] X 109/L | 28 | 36 | 0.29 |
| Blast % [median] | 2 | 13 | 0.47 |
| LDH [median] | 422 | 709 | 0.12 |
| JAK2V617F mutation, n (%) | 1/7 (14) | 7/9 (78) | 0.04 |
| Bone marrow Cellularity, n (%): - Hypercellular - Normocellular - Hypocellular | 8 (100) | 13 (65) 4 (20) 3 (15) | 0.07 0.29 0.54 |
| ↑erythropoiesis, n (%) | 7 (87) | 2 (10) | <0.01 |
| Left shift, n (%) | 5 (62) | 6 (30) | 0.20 |
| ↑granulopoiesis, n (%) | 8 (100) | 5 (25) | <0.01 |
| Left shift, n (%) | 8 (100) | 9 (55) | 0.01 |
| ↑megakaryopoiesis, n (%) | 7 (87) | 16 (80) | 1.00 |
| Micromegakaryocytes, n (%) | 7 (87) | 18 (90) | 1.00 |
| ↓megakaryocyte nuclear lobulation, n(%) | 7 (87) | 12 (60) | 0.21 |
| Clustering of megakaryocytes, n (%) | 5 (62) | 13 (65) | 1.00 |
| BM blast % [median] | 33 | 14 | <0.01 |
| % of blasts CD34 + [median] | 100 | 30 | 0.23 |
| % of blasts + for megakaryocyte markers [median] - CD61+ - CD41+ - Factor VIII+ | 30 20 20 | 100 75 50 | 0.02 0.10 0.01 |
| Reticulin fibrosis ≥ 3+, n (%) | 5 (62) | 9 (45) | 0.67 |
| Complex karyotype, n (%) | 4(50) | 10(50) | 1.00 |
| Treatment, n (%) - Induction chemotherapy - Hypomethylating agent - Clinical trial - Supportive care | 4 (50) 0 0 4(50) | 10(50) 2(10) 2 (10) 6(30) | |
| Allogeneic bone marrow transplant, n (%) | 3 (38) | 3 (15) | |
| Overall survival in months (median) | 8.67 | 7.61 | 0.82 |
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.
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