Letter to the editor: Lymphoid blastic crisis in Ph‐negative chronic myeloid leukemia

Abstract

The controversy about the origin of the blast cells in one case of Ph-negative CML blastic crisis [ 11 encouraged us to report the following observation recorded in our department 10 years ago. A 63-year-old man presented in 1975 with anemia (8 g/dl), normal platelet count, and leukocytosis of 180,000/mm3, with 1 % blast, 5% promyelocytes, 20% myelocytes, 28 % metamyelocytes, 30% stabs, 12 % neutrophils, 3 % lymphocytes, and 1 % basophils. The leukocyte alkaline phosphatase (LAP) score was nil; bone marrow aspiration revealed severe myeloid hyperplasia, a normal amount of normoblasts and megakaryocytes, and a small percentage of normal plasma cells. Repeated chromosome analysis showed a normal karyotype 46,XY and did not reveal a Ph chromosome. Serum protein level was elevated, and a narrow M component of 3.9 g/dl was demonstrated in the gamma region, which, on immunelectrophoresis, was identified as IgG kappa. No osteolytic lesions were seen on skeletal Xrays. The patient was treated with busulfan. Eighteen months later, he presented with blastic crisis. Hemoglobin was 9.2 g/dl, WBC 85,000/mm3 (including 82 % blasts), and platelet count 45,000/mm3. The bone marrow showed a diffuse infiltrate by blasts and very few residual normal hemopoietic cells. The blast cells had the morphology of large lymphoblasts with vacuoles (L3). Peroxydase, chloroacetate, and a-naphthylacetate esterases and PAS stainings were all negative. Electron microscopy analysis showed a round nucleus with few heterochromatin and one large nucleolus, polyribosomes and mitochondria in the cytoplasm, confirming the lymphoblastic type of the cells. The immunalogical studies revealed that all the blasts bore surface membrane immunoglobulin of IgM kappa type and were E rosette-negative. The karyotype during the blastic crisis was 46,XY t CI2-Dl5. The patient was treated by chemotherapy, which included vincristine 2 mg and prednisone 100 mg and responded with a decrease of WBC to 23,000/mm3 during the first 5 days. He died on the sixth day from septic shock.In this case, the occurrence of nonmyelomatous monoclonal gammopathy was an unusual finding reported only on few other occasions [2,3]. The blast cells had morphological, cytochemical, and EM features of lymphoblasts. Moreover, the immunological studies performed at that time (1977) allowed us to characterize the blast cells as belonging to a B-cell clone bearing IgM kappa surface immunoglobulin with chromosomal marker that appeared during the blastic crisis. Ph-negative CML is a very rare disease thought to be a "nonentity" by some authors [4]. This case, together with the case reported by Hughes et a1 [5] and probably the case reported by Kessler et a1 [ 13, supports the evidence that Ph-negative CML may progress to a lymphoblastic crisis as well as PH + CML.

Lymphoid Blast Crisis in a Patient with Philadelphia-Chromosome-Negative Chronic Myelocytic Leukemia

“…They also respond well to VP therapy [25,26]. In Ph-negative CML, lym phoid blast crisis is rarely reported [11][12][13][14], The rarity of cases that conform to the current criteria of Phnegative CML may have hampered any in-depth de scription of the features of blast crisis in such cases. If any common pathological mechanism is involved in the occurrence of both Ph-negative and positive CML, the acute phase might follow a similar pattern.…”

“…Although some controversy still remains [5], the current concept of Ph-negative CML is that without apparent cytogenetic changes, the same molecular event can exist as Ph-positive CML and that the clini cal and the hematological features of the chronic phase are also identical to those in Ph-positive disease [6][7][8][9][10], However, the subsequent clinical course of Phnegative CML is still unknown. Only a few cases of Ph-negative CML that developed lymphoid blast cri sis have been previously reported [11][12][13][14]. Its inci dence, phenotype and molecular aspect have not yet been clarified.…”