Hypoplastic leukemia, considered as a form of atypical leukemia has been rarely reported in the literatures. It usually affects elderly patients. Even though hypoplastic acute lymphoblastic leukemia has been reported in younger age groups, hypoplastic acute myeloid leukemia (AML) has been rarely reported in children and younger age groups. Here, we report three cases of AML with a hypocellular marrow in younger age groups. Keywords: Atypical leukemia, hypocellular marrow, hypoplastic leukemia
Acute leukemia presenting with hypocellularity has been known to occur, although rare. The term “hypoplastic leukemia” has been accepted as a different entity. Some authors are of the opinion that hypoplasia could mean a morphologic marker of good prognostic indicator. [1] The occurrence of hypoplastic acute leukemia has been widely recognized as an atypical leukemia. [2] It is characterized by pancytopenia and hypocellularity of the bone marrow (BM) containing equal to or more than 30% blast along with the absence of tissue infiltrates and or tumor masses. [3] Hypoplastic leukemias usually occur in adults. [4] Here, we report three rare cases of hypoplastic acute myeloid leukemia(AML) in young patients.
Case 1 A 17-year-old male presented with fever, pallor, and easy fatigability for 1 month. On examination, he had pallor. Organomegaly or lymphadenopathies were absent. Complete blood count (CBC) showed a hemoglobin of 6.8 g/dl. Total leucocyte count (TLC) of 3000/cumm, differential leukocyte count (DLC) showed P-18%, L-69%, E-3%, myelocytes-3%, atypical cells-7%. Platelets-30,000/cumm. BM aspiration cytology showed markedly hypocellular marrow with the scattered fragment [Figure 1]. Hypocellular (30%), erythropoiesis, myelopoiesis, and megakaryopoiesis were markedly suppressed. DLC showed blast-33%, promyelocyte-2%, myelocytes 2%, polymorphs-10%, E-1%, lymphocytes 50%. Myeloperoxidase (MPO) and Periodic acid-Schiff were negative. A diagnosis of hypoplastic leukemia was given. The lineage whether it was myeloid or lymphoid could not be ascertained. Repeat BM aspiration was done and showed similar findings.
Patient was referred to a tertiary cancer hospital where BM biopsy was done. BM biopsy showed the presence of blasts with myelofibrosis and increased number of megakaryocytes and suppressed the erythropoiesis. Immunophenotyping was done and showed CD13 positive (89%), CD33 positive (88%), CD117 positive (94%), CD34 positive (86%), HLA-DR positive (88%). However, B cell markers like CD7 (93%) were negative. A diagnosis of AML-M0 (FAB) was made. Case 2 A 22-year-old female presented with fever, throat pain, and hoarseness of voice for 1 month. On examination, patient was febrile. Organomegaly or lymphadenopathies was absent. CBC showed a hemoglobin of 3.2 g/dl. TLC of 2080/cumm, DLC-showed P-43%, L-48%, M-4%, E-3%, atypical cells-2%. Platelets-40,000/cumm. Erythrocyte sedimentation rate (ESR)-138 mm 1 st h. Red blood cells (RBC) morphology is normochromic and normocytic. Other investigations like liver function test, kidney function test were within normal range. BM aspiration showed markedly hypocellular marrow [Figure 2]. Erythropoiesis and megakaryopoiesis were markedly suppressed. Leukopoiesis showed myeloblast-15%, pormelocyte-26%, myelocyte-5%, metamyelocyte-4%, polymorphs-15%, lymphocytes-35%. MPO was positive. A diagnosis of hypoplastic acute leukemia-AML-M3 was made.
Case 3 A 10-year-old boy presented with epistaxis, fatigue, and low-grade fever for the last 3 months. Hepatosplenomegaly was detected on examination along with bony tenderness. CBC showed a hemoglobin of 5.2 g/dl. TLC of 2400/cumm, DLC-showed P-30%, L-58%, M-2%, E-2%, atypical cells-8%. Platelets-50,000/cumm. ESR-124 mm 1 st h. RBC morphology is normochromic and normocytic. BM aspiration showed markedly hypocellular marrow. Erythropoiesis and megakaryopoiesis were markedly suppressed. Leukopoiesis showed myeloblast-10%, pormelocyte-24%, myelocyte-16%, metamyelocyte-17%, polymorphs-10%, lymphocytes-23%. MPO was positive. A diagnosis of hypoplastic acute leukemia-AML-M3 was made.
The infrequent occurrence of hypoplastic acute leukemia has been recognized as an atypical leukemia defined as hypocellular marrow with ≥20% blasts and no or few blast in the circulating blood. [5] We are reporting three rare cases of hypoplastic AML for the 1 st time in our institute and the state of Manipur. Usually, hypocellular acute lymphoblastic leukemias occur in children. [4] Hypoplastic AML has been rarely reported in pediatric and young patients. However, only two cases of hypoplastic AML have been reported in young patients in India. [6] The diagnostic criteria have been proposed by Nagai et al. [7] with the following features: Pancytopenia with a rare appearance of blast in peripheral blood; <40% BM cellularity; more than 30% blasts in the BM of all nucleated cells and myeloid phenotypes of leukemic blasts by MPO staining and/or immunophenotyping. All the criteria were fulfilled in our three cases. Tuzuner et al. revealed a preponderance of FAB-M1 category followed by M2 and M6 types. [8] In a report of two cases in India, all were of M1 subtype. But our first case was M0 subtype, and the other two were of M3 subtype. Literature regarding M3 subtype is very rare though Kojima et al. [9] reported hypocellular acute promyelocytic leukemia with a tetraploid clone. Though the pathogenesis of hypocellularity still remains speculative, it seems clear that these patients bear a lower leukemic burden and experience a more indolent course and can commonly achieve a good response to remission induction therapy. [1],[10] However, two mechanisms have been proposed. First, it has been suggested that leukemia cell populations inhibit myelopoiesis through a humoral mechanism. [11] Second, an increased susceptibility of myeloid precursors to the inhibitor in older patients might play a role in the genesis of hypoplasia. [1] Recent reports suggest the beneficial effects of granulocyte colony-stimulating factor in the hematopoietic reconstruction following chemotherapy. [12]
Hypoplastic AML can occur in young patients though rare. Larger study is the need of the hour to bring into light the exact prevalence of this condition.
Source of Support: None, Conflict of Interest: None
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