TRANSFORMATION OF MYELODYSPLASTIC SYNDROME TO T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA IN A YOUNG ADULT

A 20-year-old male presented with a 1-month history of pallor, weakness, and fatigue. There was history of gum bleeding and petechial spots over body for last 15 days. He received 5 units blood transfusion outside. On examination, he was pale. Spleen was enlarged 2 cm below costal margin. Liver was not enlarged. His hemoglobin (Hb) was 70 g/L, total leukocyte count (TLC) 1.6 × 10⁹/L, and platelet count was 14 × 10⁹/L. Peripheral smear showed normocytic and macrocytic RBCs. No abnormal cells were noted. Bone marrow aspirate was cellular with dysmyelopoiesis and dysmegakaryo- poiesis. Blasts were 15%. A diagnosis of myelodysplastic syndrome (MDS)-refractory anemia with excess blasts (RAEB-2) was made.

One month later he presented with abdominal distension. He had developed bilateral axillary lymph node enlargement. Liver was palpable 5 cm and spleen was 16 cm below costal margin. There was bilateral lower motor neuron facial nerve palsy. His TLC had increased to 78 × 10⁹/L. The bone marrow aspirate showed total replacement with blasts, which were negative for myeloperoxidase, Sudan black, and PAS. Immunophenotype revealed that these blasts were positive for CD2 and CD7 and negative for B-cell and myeloid markers. A final diagnosis of MDS-RAEB with transformation to T-cell ALL (T-ALL) was made. Cerebrospinal fluid analysis was normal.

He was started on BFM 83 protocol and achieved complete remission with prednisolone, daunorubicin, vincristine, and l-asparginase in 4 weeks. Consolidation chemotherapy included cyclophosphamide, cytosine arabinoside, and etoposide and weekly intrathecal methotrexate every 8 weeks followed by maintenance chemotherapy. He received 18 Gy cranial irradiation. Central nervous system prophylaxis was given in the form of intrathecal methotrexate 12.5 mg every 3 months during maintenance. High-dose methotrexate was not given. He is about to complete his maintenance chemotherapy and has been well for the last 3 years.

Evolution of MDS into ALL is rare. Twenty-four cases of MDS transformation to ALL have been described in literature (Table 1) [[1], [2], [3], [4], [5]]. The median age of transformation was 65 years (15–78 years). There has been a dramatic male preponderance, with 19 males and 5 females (details for 1 not available). The different types of myelodysplasia had been MDS RA 39% (9/23), RAEB 35% (8/23), and RARS in 22% (5/23) and 4% (1/23) in CMML. The median time to transformation was 5 months (2–50 months). There has been no specific predilection to B-cell or T-cell subtype with 52% (11/21) B-cell, 43% (9/21) T-cell, and 5% (1/21) null phenotype. Different cytogenetic aberrations varying from normal to complex has been reported. Six (6/17) patients had normal cytogenetics. Eight (8/20) patients were refractory or died early in induction. A total of 10/20 achieved CR and 2 achieved PR. Patients with T-cell transformation faired better than those with B-cell ALL. There were 63% (5/8) CR, 12% (1/8) PR, and 25% (2/8) deaths in T-cell ALL.

TABLE 1 Patient Characteristics and Outcome in Cases of MDS Transformation to ALL

				Time to
	Age		MDS	progression
S No.	(years)	Gender	subtype	(months)	Phenotype	Cytogenetics	Outcome
1	68	M	RARS	31	B cell	+8	Expired
2	9	M	RA	21	B cell	NA	Lost
3	68	F	RAEB	5	B cell	−3,5q-	Expired
4	54	M	RA	30	B cell	Ph, 20q-	Expired
5	50	M	RA	4	B cell	Complex	CR
6	43	M	NA	NA	B cell	Complex	Expired
7	46	M	RAEB	2	B cell	NA	CR
8	70	M	RA	22	B cell	NA	NA
9	68	F	RA	2	B cell	NA	NA
10	65	M	RA	18	B cell	+13	PR
11	28	F	RA	11	B cell	Normal	Refractory
12	65–72	5 M, 1 F	1 RA, 2 RARS, 3 RAEB	4–18	T cell (All 6)	Variable	2 Expired, 4 CR
13	75	M	RAEB	18	T cell	Normal	NA
14	53	M	CMML	42	T cell	Normal	PR
15	53	M	RARS	50	Null cell	NA	CR
16	Elderly	M			NA	NA	NA
17	58	M	RA	20	NA	NA	Expired
18	50	F	RAEB	3	NA	Normal	Well (5 years)
19	67	M	RARS	24	NA	Aneuploidy	CR
Our case	20	M	RAEB	5	T cell	NA	CR (2 years)

Note. CR, complete remission; PR, partial remission; NA, not available; RA, refractory anemia; RARS, refractory anemia with ring sideroblasts; RAEB, refractory anemia with excess blasts; CMML, chronic myelomonocytic leukemia; MDS, myelodysplastic syndrome.

The median time to progression to ALL is only 5 months. The remission rates and survival rates are better, more so for T-cell ALL as compared to AML.

Declaration of Interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.