CD2 expression in acute promyelocytic leukemia is associated with microgranular morphology (FAB M3v) but not with any PML gene breakpoint.

In the t(15;17) translocation of acute promyelocytic leukemia (APL) at least three regions of the PML gene are involved in the reciprocal translocation between the PML and the RAR-alpha loci. The chimeric PML/RAR-alpha fusion transcripts can be demonstrated in all cases of APL, by a specific reverse-transcription PCR (RT-PCR). Previous studies found a correlation between expression of CD2 and involvement of the PML bcr3. In this study, we assessed this association in 43 children and adults with APL. A blind morphologic review of all smears was performed by four experienced hemopathologists who agreed the diagnosis of M3 vs M3v APL. CD2 expression on APL was detected by using different monoclonal antibodies (MoAbs) directed against specific CD2 epitopes by flow cytometry and in selected cases by Northern blot by the use of a specific CD2 cDNA probe. Nineteen of 43 cases displayed the typical microgranular features consistent with the diagnosis of M3v. Of these, 12 had the bcr3 breakpoint on chromosome 15, while seven had the bcr1 type. In 16 of the 19 patients, leukemic cells expressed both CD2 protein and the corresponding mRNA. Similarly, in the negative cases, Northern blot analysis failed to demonstrate the presence of specific mRNA. The remaining 24 patients, with the classic morphologic features of M3, were CD3 negative. These results point out that CD2 expression correlates with the FAB M3v and not with the PML breakpoints. During the course of all-trans retinoic treatment a down-modulation of CD2 expression was observed in three M3v cases. Overall, our findings might suggest a role of CD2 epitopes in the regulation of adhesion properties of APL blast cells.

Extramedullary blast crisis in chronic myeloid leukemia.

Among 235 patients with CML we reviewed 91 patients with BC diagnosed between 1980 and 1995; 15 of the 91 (16%) developed extramedullary disease (EMD). The sites involved were the lymph nodes (13/15), CNS (1/15) and suborbital mass (1/15). The appearance of EMD was associated with chronic phase (CP) features in the bone marrow in 3/15 cases, with accelerated phase (AP) in 3/15 and with BC in 9/15. 11/15 (73%) cases of EMD were classified as myeloid (My-EMD) and 4/15 as lymphoid-type (Ly-EMD): three B-phenotype and one T-phenotype. All Ly-EMD cases were treated with vincristine, daunorubicin and prednisone and obtained complete remission (CR). Cases of My-EMD were treated with daunorubicin and cytosine arabinoside, of which only 1/11 achieved CR. We suggest that in EMD also, the type, lymphoid or myeloid, of BC has a bearing on treatment response and prognosis: Ly-EMD is more responsive to treatment and has longer survival than My-EMD.

Ph positive acute lymphoblastic leukemia in adults: molecular and clinical studies.

Fifty-six patients with ALL were investigated for bcr involvement by PCR. Breakpoints were found in 15 patients (26.8%). There were no differences in clinical and hematologic features or the percentages of complete response (CR) between the Ph+ and Ph- cases. The duration of CR was 6 and 8 months, respectively. In 7/9 Ph1 relapsed ALL we observed increased expression of myeloid markers and 2/9 showed a switch of cytotype (Ly-->My). In none of the 13 Ph- relapsed ALL patients did we observe these findings. 7/15 of Ph+ cases expressed P190 and mRNA ela2 and 8/15 patients showed P210, with mRNA b3a2 in 5 and b2a2 in 3, respectively. The percentage of CR was 57% in the P190+ and 87% in the P210+ group. Investigation of more Ph1+ ALL cases treated with a uniform protocol should be performed in the future in order to determine whether any such biological and clinical differences exist.

Rare phenotype and transplantability in cadaveric kidney transplant.

The waiting list for kidney transplants in the Apulia region contains recipients (about 30%) who were never selected for transplant due to the rare HLA antigen phenotypes and homozygosis. Therefore, an algorithm was selected to equilibrate the chance for patients to be selected despite a rare phenotype. We calculated for each patient, the sum (%) of the A, B, DR antigen frequency (total phenotypic frequency; TPF). All the potential recipients were grouped into five classes in increasing order of TPF. The number transplanted depended on the phenotype frequency. The selection index was the quotient of the number selected and the total number of patients. The selection index was 0.28 to 0.43 to 0.79 to 1.34 to 2.38 from class 1 to 5. To equilibrate the transplantability of rare phenotype recipients on the waiting list, a bonus was introduced for the most disadvantageous frequency class. Adding the bonus modified the selection index as follows: 1.0 to 1.25 to 1.5 to 1.34 to 2.38, which appears more equilibrated except for the class 5. In conclusion, if a bonus is applied for rare phenotypes, the chance to be transplanted becomes similar between patients with other parameters the same.

Extramedullary involvement in patients with acute promyelocytic leukemia: a report of seven cases.

BACKGROUND: Extramedullary involvement is only occasionally observed in patients with acute promyelocytic leukemia (APL) but has been said to occur more frequently after treatment with all- trans retinoic acid (ATRA) than after treatment with cytotoxic drugs. In the literature, 37 well-documented cases have been reported. METHODS: The authors report 7 patients with extramedullary APL documented by cytologic, phenotypic, and molecular analyses among 120 adult APL patients referred to two different institutions during a period of 9 years. RESULTS: In this APL series, extramedullary disease (EMD) occurred in 7 of 120 cases (5.8%). The extramedullary sites were the skin in five patients, the central nervous system in one, and the lymph nodes in one. Molecular analysis of the PML/RARalpha rearrangement was performed on four samples of skin and one of CSF; all patients exhibited the same molecular pattern in the bone marrow (BM) and EMD sites. Of 120 patients, 61 were treated with ATRA plus chemotherapy and 59 with chemotherapy alone. Relapses were observed in 38 patients, 6 of whom had EMD; 1 patient had developed EMD at the onset of APL. Of the relapsed EMD cases, 2 of 61 patients had received ATRA plus chemotherapy and 4 of 59 had received chemotherapy alone. CONCLUSIONS: There is some controversy as to whether treatment of APL with ATRA may predispose patients to the development of extramedullary relapse. The data from this study do not contain evidence that EMD may occur more frequently in APL patients treated with ATRA.