L.C. Chan

The Spectrum of Chronic Lymphoproliferative Disorders in Chinese People

Background. Chronic lymphoproliferative disorders are considered rare in Oriental patients and are thought to constitute only 2% of all leukemias in these patients, compared to 20‐30% in Western patients. We conducted a retrospective analysis of Chinese patients with chronic lymphoproliferative disorders to define the frequency and spectrum of these disorders.

Pure red cell aplasia : Clinical features and treatment results in 16 cases

Abstractu2002Pure red cell aplasia (PRCA) is a rare hematological disease characterized by selective marrow erythroid aplasia. We report the clinical features and treatment results of 16 Chinese patients with PRCA. Nine (56%) cases were not associated with any underlying disorders and were considered idiopathic, while seven patients (44%) had associated diseases, three involving the thymus, two with T large granular lymphocyte leukemia (T-LGLL), and one each with Stevens-Johnson syndrome and acute hepatitis A. Conventional-dose corticosteroid therapy resulted in complete remission in three of 13 patients. Cyclosporin A was used in six patients. There were three complete and one partial remissions. High-dose methylprednisolone was ineffective in four patients who failed conventional-dose corticosteroids but achieved complete remission in one patient with thymoma who did not respond to thymectomy. Antithymocyte globulin was used in four patients, resulting in partial remission in only one patient with concomitant T-LGLL. Intravenous gamma globulin and danazol were ineffective in three patients. Thymectomy was performed in two patients, with one patient remitting. This is the largest series of PRCA reported in an oriental population. Our results indicate that treatment of PRCA may still be problematic and better therapeutic strategy will have to be defined.

Trisomy 12 in chronic lymphocytic leukemia: An interphase cytogenetic study by fluorescence in situ hybridization

B-cell chronic lymphocytic leukemia (CLL) is a rare disorder in the Chinese population. We evaluated the use of fluorescence in situ hybridization (FISH) with a chromosome 12-specific probe in the detection of trisomy 12 in interphase cell of 19 Chinese CLL patients. FISH successfully detected trisomy 12 in two cases, one of which had normal conventional cytogenetic findings, giving an incidence of 10%. The low incidence of trisomy 12 in our CLL patients may also reflect a biologic difference of this rare disorder in our population, compared to that of the West.

Cytogenetic triclonality in acute myeloid leukemia: A morphologic, immunologic and in situ hybridization study

Cytogenetically unrelated clones are uncommon in hematologic malignancies. We report a case of acute myeloid leukemia, which consisted morphologically of two populations of small and large blasts demonstrating immunophenotypic heterogeneity. Cytogenetic analysis showed 3 karyotypically abnormal clones: 47,XY, +14/45,XY,dic(5;17)(q11;p11),14dmin, and a near-tetraploid clone. In situ hybridization showed that the near-tetraploid clone corresponded to the large blasts, and the near-diploid clones the small blasts, therefore demonstrating a direct relationship between cell size and DNA content. The diverse morphologic, immunologic and cytogenetic heterogeneity observed in our case suggested hematopoietic oligoclonality.

Trisomy 4 may occur in a broad range of hematologic malignancies

Trisomy 4 is an uncommon numerical chromosomal aberration in acute leukemia. We describe three cases of trisomy 4, occurring in two patients with acute myeloid leukemia (M1 and M5a) and in one patient with T-cell acute lymphoblastic leukemia. Our results suggest that trisomy 4 may occur in a broader range of hematologic and malignancies than previously described.

Robertsonian translocation as an acquired karyotypic abnormality in leukaemia

Robertsonian translocations, although relatively common as a constitutional genetic aberration, are rarely encountered in leukaemia. We report a case of acute myeloid leukaemia which showed an acquired Robertsonian translocation in the form of der(14;21) by cytogenetic analysis of leukaemic cells. This was confirmed by the PHA‐stimulated culture of peripheral blood lymphocytes. A review of the literature identifies only eight reported cases of acquired Robertsonian translocations in leukaemia. In the majority of cases the Robertsonian translocation occurs as a secondary change in a complex abnormal clone, whereas in two out of nine patients reported, including ours, it is found as a sole karyotypic abnormality.

Interstitial Deletion of 9q Revisited

Interstitial deletion of the long arm of chromosome 9 (9q-) is an uncommon karyotypic abnormality in acute myeloid leukemia (AML). We report a case of acute myeloid leukemia, M6 according to the FAB criteria, in which 9q- was the sole karyotypic abnormality. From our own experience and that in the literature, interstitial 9q- seems to be associated with two specific morphologic/cytogenetic categories: AML M2 and t(8;21)(q22;q22)/trisomy 21; and as the sole karyotypic aberration in AML M1/M2(M6) with dyserythropoiesis. Examination of the published karyotypes shows that 9q13 to 9q21 is the commonest deleted segment, suggesting that this region may carry genes important in leukemogenesis.

A novel translocation (3;11)(q26;q13) in a case of acute myelomonocytic leukemia.

We report a novel translocation (3;11)(q26;q13) in a case of acute myelomonocytic leukemia. The implications of rearrangements involving chromosomes 3q26 and 11q13 are discussed.

Allogeneic bone marrow transplantation for adult acute lymphoblastic leukemia: a single-centre experience.

Between 1990 and 1997, we performed 29 allogeneic BMTs for acute lymphoblastic leukemia (ALL) patients with HLA‐identical sibs. Their median age was 31 years (range 15 to 43); there were 15 males and 14 females. The conditioning protocol was Cy‐TBI (n=15), VP16‐Cy‐TBI (n=12), CBV (n=1) and Bu‐Cy (n=1). Cyclosporin and methotrexate were used for GVHD prophylaxis. The median disease‐free survival (DFS) was 12 months (range 1 to 92) with an actuarial 4‐years DFS of 42·3 per cent. Three patients died of transplant‐related complications before 100 days. Relapse occurred in 11 cases at a median time of 5 months (range 3 to 14). All nine patients relapsing within one year died form resistant leukemia. Three patients died of late treatment‐related complications. There were 13 survivors (median follow‐up 38 months, range 12–98), with 12 in remission. Only four had limited cGVHD, and all had 100 per cent performance scores. One patient also cleared her chronic hepatitis B carrier status due to acquired immunity. The DFS rates amongst CR1 cases and R1/CR2 cases were comparable (p=0·39). No long‐term DFS is obtained from patients with resistant disease (n=4). The survival results for BMT at CR1 were superior to those using intensive chemotherapy consolidation (p=0·29), mainly due to poor late results in the chemotherapy arm. For young ALL patients with HLA‐matched siblings, the option of BMT should be considered in light of local consolidation survival results. Copyright

Dual-color flow cytometric analysis of megakaryocytic DNA ploidy in the investigation of blastic phase chronic myelogenous leukemia with rearrangement of 3q26

A patient is described with chronic myelogenous leukemia in blastic crisis, in whom numerous circulating platelet fragments and megakaryocytic nuclei were present, with 50% blasts and 50% micromegakaryocytes in the marrow. The blasts expressed myeloid‐associated antigens CD34, CD33, and CD13, whereas the micromegakaryocytes were positive for CD41, CD42b, and CD61. These findings suggested a myeloblastic transformation with a possible megakaryoblastic component. Cytogenetic analysis showed rearrangement of 3q26 in the form of t(2;3) (p13;q26), in addition to t(9; 22) (q34; q11). Dual‐color flow cytometric analysis of DNA content of CD42b‐positive cells showed that the micromegakaryocytes were predominantly 2N, indicating a maturation block before nuclear endoreplication and polyploidization. These findings confirmed a combined myeloblastic and megakaryoblastic transformation. It is concluded that dual‐color flow cytometric DNA analysis is a useful method for the investigation of abnormal megakaryocytopoiesis in hematologic malignancies.