Aleukemic Leukemia: A Rare Presentation

Introduction

Aleukemic leukemia is a type of leukemia where the blasts are not evident in peripheral blood while they can be found in marrow. Here we present a case of an eight-year-old boy who reported with fever. A detailed workup led to the diagnosis.

Case Presentation

An eight year old boy presented with complaints of high grade fever for 15 days, history of bilateral lower limb pain, decreased appetite, weight loss and easy fatiguability. Physical examination revealed pallor, bilateral inguinal lymphadenopathy, hepatosplenome-galy (Liver and spleen 5 cm below costal margin) and ejection systolic murmur. No skin lesions or bleeding manifestations were noted.

Initial blood count showed hemoglobin of 6 g/dL, total leucocyte count of 2900 cells/dL, with 16% neutrophils, 80% lymphocytes, platelet count of 2.27 lakh / cu mm and ESR of 17 mm. Peripheral smear examination showed severe normochromic to microcytic hypochromic anemia with neutropenic leukopenia, one atypical cell, neutrophils 8%, lymphocytes 89%, monocytes 3%, with no basophils and adequate number of platelets (Figure 1). Coagulation profile showed prothrombin time (control: 11.5 seconds/test: 14 seconds), partial prothromboplastin time (control: 26.8 seconds/test: 29.3 seconds) and international normalised ratio (INR) (1.21) to be normal.

Liver and renal function tests were normal. Serum lactate dehydrogenase (393 units/L) levels and serum ferritin (859 ng/mL) levels were elevated. Serum uric acid was 3.2 mg/dL. Blood culture showed no growth. Ultrasound of abdomen revealed hepatosplenomegaly with normal texture.

After ruling out infectious causes for fever, bone marrow study was done. Bone marrow aspiration yielded a dry tap and could not be interpreted. Bone marrow biopsy was suggestive of acute myeloid leukemia (few scattered atypical blast cells) (Figure 2).

Considering the diagnosis to be Acute Myeloid Leukemia - M3 type, PML-RARA (promyelocytic leukemia/ retinoic acid receptor alpha) test was conducted which came negative (AML gene not detected).

Bone marrow aspiration was repeated which showed blast cells, suggestive of acute leukemia (Figure 3). Flow cytometry analysis suggested T-Lymphoblastic Leukemia, T-ALL with 55% blast cells and other T cell markers [(Aberrancy detected - CD33 and CD 56) with bright expression of CD7 (97)].

Bone marrow was a diluted sample and hence, taking the clinical features, total count levels and flow cytometry report into consideration, T- ALL was confirmed and child was started on BMF -90 protocol chemotherapy. Child tolerated the initial cycles of chemotherapy.

Discussion

Acute lymphoblastic leukemia (ALL) is a heterogeneous hematologic disease characterized by the proliferation of immature lymphoid cells in the bone marrow, peripheral blood, and other organs.¹ It accounts for 75–80% of paediatric leukemia and is the most frequent paediatric malignancy. Indian incidence varies with geography and age-adjusted rates of up to 101.4 per million and 62.3 per million for boys and girls, respectively have been observed.^2,3 The incidence of ALL is significantly higher in males and peaks between 2 - 5 years. T cell ALL includes about 15-20% of paediatric ALL. Yet in India, a greater proportion of T-ALL (20-50%) has been recorded.³

Failure of bone marrow or invasion of leukemic cells, both result in clinical symptoms. The most typical presenting symptoms are bone-joint pain, fatigue, lethargy, persistent fever, bruising, and bleeding. Other features include organomegaly, lymphadenopathy, symptoms of CNS involvement (headache, vomiting and cranial nerve palsy), mediastinal mass (T cell ALL).⁴

Examination of the bone marrow and peripheral blood can confirm the diagnosis. A diagnosis of acute leukemia alone, however, is insufficient because each type of neoplasm has a markedly different course of treatment and outlook. Depending on the instance, further classification may require cytochemistry, flow cytometry, cytogenetic, and molecular biologic studies.⁴

The diagnosis of ALL requires demonstration of ≥20% bone marrow lymphoblasts on hematopathology, review of bone marrow aspirate and biopsy materials. Presentations of ALL with low blast counts are uncommon. 

The present case had persistent fever and history of weight loss, implying the need to rule out infections. With physical examinations and adequate laboratory tests, infectious causes were excluded and malignancy was considered. As the blood smear examinations did not show blasts, bone marrow studies were required for the diagnosis. As the bone marrow showed atypical cells, diagnosis of aleukemic leukemia was considered.

In acute leukemia, the bone marrow and peripheral blood both typically include blast cells, where-as aleukemic leukemia occurs when the peripheral blood has fewer or no blast cells and the bone marrow meets the criteria for acute leukaemia.⁴

The absence of leukemic appearance in peripheral blood, along with an abnormal marrow blast morphology posed diagnostic difficulties in this patient. As a result, it becomes challenging to distinguish ALL from an uncommon proliferation of hematogones, and cytogenetic testing became an important step in confirming the final diagnosis.⁵

This case demonstrates that unexplained cytopenias may be the first sign of acute leukemia, before circulating blasts can be detected. Comprehensive investigations are needed and cytogenetic findings may offer important diagnostic information in addition to their well-recognized prognostic value.

This case demonstrates that unexplainable cytopenias may be the initial sign of acute leukemia, before circulating blasts can be found. Cytogenetic data, in addition to their well-known predictive importance may also provide crucial diagnostic information. Therefore thorough investigations are required.⁵

Summary

In summary, we have reported a paediatric case of Aleukemic T-lymphoblastic leukemia presenting with persistent fevers. Aleukemic leukemia is a rare entity requiring high index of suspicion. Every effort should be made to arrive at a correct diagnosis. Patients should be evaluated with bone marrow examination to rule out leukemia when the clinical features cannot be explained by other diseases.

Conflicts of Interest

Nil