We studied minimal residual disease in 6 patients with Philadelphia positive acute lymphoblastic leukemia (Ph1 ALL) in remission by using a combination of cell sorting (CD34 + ) and FISH. The detection of residual leukemic cells in Ph1 ALL by using this method is much more sensitive than conventional morphology and cytogenetic analyses.

We wish to comment on the article by Stefan Lohmander in which the results of a placebo controlled study with intra-articular hyaluronan in osteoarthritis of the knee were presented.1It was suggested that aged …

The authors review the main cytogenetic abnormalities encountered in MDS particularly del 5q, -7, +8, and complex abnormalities. Their presence may be useful to the diagnosis of MDS in difficult cases. Their prognostic value is important, and cytogenetics have recently been included in prognostic scores in MDS. Knowledge of recurrent chromosomal rearrangements is finally a first step in the discovery of genes implicated in the pathogenesis of MDS.

A familial lympho-epithelial thymoma with constitutional chromosomal translocation t (14;20) (q24;p13) is presented: the thymoma and its particular translocation are present in the mother and the two sons of her offspring. The small number of cases do not allow establishing any relation between thymoma and this particular translocation. Concerning genetic counseling, an annual thoracic radiography is necessary for all the other family members, carriers or not of the translocation.

Seventy-seven elderly patients (median age 72, range 59–85) with de novo AML were treated with lowdose Ara C (10 mg/m2/12 h over 21 days, for one or two courses). Thirteen (17%) achieved complete remission (CR), 16 (21%) partial remission (PR); 28 (35%) had resistant leukemia, and 20 (26%) early death or death during hypoplasia. Most (86%) of the patients had severe pancytopenia and 58% were hospitalized. Overall median survival was 3 months. Median duration of CR was 9 months. Five CR were longer than 1 year, and two were longer than 4 years. All but one PR were ≤9 months, and 12/16 were ≤4 months. Karnofsky index and karyotype (the latter performed for 52 patients) were the only significant prognostic factors of response to treatment (including CR + PR) and survival: poor response rate (8%) and survival (median 0.7 months) were found in patients with Karnofsky index < 60, compared with 44% and 4 months, respectively, in patients with Karnofsky index ≥60; likewise, patients with rearrangements of chromosome 5 and/or 7 or complex rearrangements had a response rate of 13% and median survival of 1.5 months, compared with 68% and 8 months, respectively, in patients with normal karyotype or single abnormalities (not involving chromosomes 5, 7, or 8). Patients with isolated trisomy 8 had a response rate of 37% but short median survival (2.5 months). Significantly longer survival was seen in responders. Our findings suggest that, overall, low-dose Ara C yields limited results in AML in the elderly. However, it could remain a useful option in elderly patients with AML who are not candidates for intensive chemotherapy (even with the support of growth factors), provided their general condition is not too altered and they do not have an “unfavorable” karyotype (i.e., rearrangements of chromosomes 5 or 7 or complex abnormalities).

Sixty-three of 373 patients (17%) with de novo myelodysplastic syndrome (MDS) survived more than 5 yr (long survivors). At diagnosis, they usually had no or only moderate cytopenias; 63% of them had marrow blasts <5%; only 1 patient had circulating blasts; 60% had refractory anaemia (RA) or refractory anaemia with ringed sideroblasts (RARS); 19% of the 43 patients who were karyotyped had an abnormal clone, and only 2 patients had complex cytogenetic findings. Only 4 of the 63 patients progressed to another FAB type within 5 yr of diagnosis, from RA to refractory anaemia with excess of blasts (RAEB) or chronic myelomonocytic leukaemia (CMML). After 5 yr, 9 patients showed progression (including progression to AML in 5 patients). The other patients remained stable (43 cases) or died from cytopenias or unrelated disorders (11 cases). Except for 3 patients who achieved prolonged complete remission with intensive chemotherapy, and possibly 3 patients who responded to low dose Ara C, prolonged survival seemed to result mainly from the low natural course of the disease.Although, as expected, significant differences for age, cytopenias, circulating and bone marrow blasts, and karyotype were seen between short (<2 yr) and long (>5 yr) very few significant differences were seen between intermediate and long survivors. These 2 subgroups only differed by significantly lower age and higher haemoglobin level in long survivors. Multivariate scoring systems (Bournemouth, Sanz's and Lille scores) proved of relatively limited value in differentiating them. Thus, currently known prognostic factors in MDS are capable of identifying short survivors, but cannot as readily distinguish patients who will have an intermediate survival from truly long survivors.

We performed immunocytochemical detection of myeloperoxidase (MPO), using monoclonal antibody MPO-7, in 15 consecutive cases of adult acute leukemia (AL) unclassified by conventional cytological and cytochemical criteria and 7 AML-M1 with less than 10% of cytochemically MPO-positive blasts. In AL with negative MPO cytochemistry the anti-MPO reaction was positive in 5 of the 15 patients with 3, 3, 7, 11 and 45% positive blasts respectively. In AML-M1, immunocytochemistry was positive in a larger percentage of blasts than cytochemistry in 2 cases. Immunological detection of myeloid surface markers was positive in all 15 cases of unclassified AL (including the 10 AL with negative anti-MPO reaction). Eleven of the 22 patients from this study had mixed lymphoid-myeloid phenotype. Discrepancy between immunological MPO detection and light cytochemistry was more frequent in patients with mixed immunophenotype than in patients without lymphoid markers. No relationship between MPO-antigen positivity and clinical or biological features was seen. These findings confirm immunological detection of MPO as useful for the diagnosis of poorly differentiated AL. The high incidence of inactive MPO detectable only by immunocytochemistry in mixed lineage AL needs to be confirmed.

Although the prognostic value of cytogenetic analysis has previously been demonstrated in myelodysplastic syndromes (MDS), karyotype had not been included in previously published scoring systems, such as Bournemouth and Sanz's scores. We studied karyotype at diagnosis in 408 cases of de novo MDS (after excluding therapy-related MDS). Karyotypes were classified in 10 groups: normal; isolated del 5q; del 5q and other rearrangements; isolated +8; isolated -7 or del 7q; del 20q; isolated -Y; miscellaneous single rearrangements; -7 or del 7q and other rearrangements; miscellaneous complex rearrangements. Karyotypes were considered complex when at least three chromosomes were rearranged. Complex karyotypes included all patients with del 5q and other rearrangements, -7 or del 7q and other rearrangements, and miscellaneous complex rearrangements (i.e. three of the 10 groups). Median actuarial survival of the 408 patients was 28 months, and 90 patients (22%) progressed to acute myeloid leukemia (AML). For survival, bone marrow (BM) blasts, circulating blasts, white blood cell (WBC), neutrophil count, platelet count, hemoglobin, age, sex, FAB classification, and Bournemouth and Sanz's scores had strong prognostic value. Cytogenetics also had strong prognostic value. An unfavorable cytogenetic group (patients with complex karyotypes) was identified. On the other hand, although patients with isolated del 20q and del 5q had a somewhat better prognosis than other patients with non-complex cytogenetic findings, they could not be statistically individualized as a favorable group, possibly owing to their relatively limited number. By multivariate regression analysis, a three-variable new scoring system could be designed based on karyotype (1 point for complex karyotype; 0 for other groups), platelets (0 for > 75 x 10(9)/l; 1 for < 75 x 10(9)/l), and BM blasts (0 for < 5%, 1 for 5-10%, 2 for > 10%). The total score (addition of points for the three variables) was able to separate patients in three groups with low (score 0) intermediate (score 1 or 2), and high risk (score 3 or 4) which included 34%, 47%, and 19% of the patients, and had a median survival of 55, 24, and 6 months, respectively (chi 2 = 110, p < 10(-4)). This new score (Lille score) was able to subdivide risk groups according to Bournemouth and Sanz's scores into further subgroups of different prognoses. For progression to AML, BM blasts, circulating blasts, WBC count, hemoglobin, FAB type, and karyotype had prognostic value by univariate analysis.(ABSTRACT TRUNCATED AT 400 WORDS)

Exons 5 to 8 of the p53 gene were examined for mutations in 60 patients with B-cell acute lymphoblastic leukemia (ALL), including 50 cases of precursor-B-cell ALL, nine cases of Burkitt (L3) ALL and one case of atypical ALL with surface immunoglobulins and t(8:14) translocation but L2 morphology. Karyotype was available in all patients. DNA was analyzed by polymerase chain reaction, single strand conformation polymorphism analysis, and nucleotide sequencing. Three patients showed point mutations in exons 7 or 8, including two of the nine patients with Burkitt ALL and one of the 50 patients with precursor-B-cell ALL. These findings suggest that p53 gene mutations are rare in precursor-B-cell ALL but may be more frequent in Burkitt ALL. In the three patients with p53 mutations, however, the relevance of those mutations to the development or progression of leukemia remained uncertain.

We report two cases of secondary acute lymphoblastic leukemia (ALL) with t (4;11) (q21;q23) translocation occurring after chemotherapy and radiotherapy for a prior cancer. Seven previously published cases of secondary ALL with t (4;11) (q21;q23) are also reviewed. Most patients had received a combination of topoisomerase II inhibitors (anthracyclines, mitoxantrone, or the epipodophillotoxin derivatives VP16 or VM26) and cyclophosphamide, which have also been implicated in the pathogenesis of secondary acute myeloid leukemia (AML) with 11q23 rearrangements. These observations give further support to the existence of a subgroup of secondary acute leukemias with cytogenetic findings "specific" for de novo ALL and AML, especially those with translocations involving the 11q23 region.

Myelodysplastic syndromes (MDS) associated with an excess of bone marrow blasts include the FAB subtypes of refractory anemia with excess of blasts (RAER), RAEB in transition (RAEB-t), and about half of the cases of chronic myelomonocytic leukemia (CMML). They have a short survival, rarely exceeding 2 years. As most of these patients are elderly, however, treatment has usually been purely symptomatic or, more recently, has utilized low-dose cytosine arabinoside (ara C) with, in spite of some encouraging results, low complete remission (CR) rates and no definite improvement in survival. Allogeneic bone marrow transplantation (BMT) has given very encouraging results [1], but this therapy is limited to the rare younger MDS patients with an HLA-identical sibling, whereas the excellent results recently obtained with recombinant granulocyte-macrophage colony-stimulating factor are still very preliminary. A place therefore seems to remain for combination chemotherapy in younger patients with MDS, capable of withstanding a long period of aplasia. We report our results with aggressive chemotherapy in 29 primary MDS patients.

British Journal of HaematologyVolume 82, Issue 3 p. 623-626 CYTOGENETIC AND MOLECULAR REMISSION IN A CASE OF ACUTE MYELOID LEUKAEMIA (AML) WITH INVERSION OF CHROMOSOME 16 (Inv(16)) AND PHILADELPHIA CHROMOSOME (Ph) Claude Preudhomme, Claude Preudhomme Laboratoire d'Hématologie, C.H.U., 1 Place de Verdun, 59037 Lille, FranceSearch for more papers by this authorJean Luc Lai, Jean Luc Lai Service de Cytogénétique, C.H.U., 1 Place de Verdun, 59037 Lille, FranceSearch for more papers by this authorIsabelle Plantier, Isabelle Plantier Service des Maladies du Sang, C.H.U., 1 Place de Verdun, 59037 Lille, FranceSearch for more papers by this authorJean Loup Demory, Jean Loup Demory Service des Maladies du Sang, C.H.U., 1 Place de Verdun, 59037 Lille, FranceSearch for more papers by this authorMarc Zandecki, Marc Zandecki Laboratoire d'Hématologie, C.H.U., 1 Place de Verdun, 59037 Lille, FranceSearch for more papers by this authorPierre Fenaux, Pierre Fenaux Service des Maladies du Sang, C.H.U., 1 Place de Verdun, 59037 Lille, FranceSearch for more papers by this author Claude Preudhomme, Claude Preudhomme Laboratoire d'Hématologie, C.H.U., 1 Place de Verdun, 59037 Lille, FranceSearch for more papers by this authorJean Luc Lai, Jean Luc Lai Service de Cytogénétique, C.H.U., 1 Place de Verdun, 59037 Lille, FranceSearch for more papers by this authorIsabelle Plantier, Isabelle Plantier Service des Maladies du Sang, C.H.U., 1 Place de Verdun, 59037 Lille, FranceSearch for more papers by this authorJean Loup Demory, Jean Loup Demory Service des Maladies du Sang, C.H.U., 1 Place de Verdun, 59037 Lille, FranceSearch for more papers by this authorMarc Zandecki, Marc Zandecki Laboratoire d'Hématologie, C.H.U., 1 Place de Verdun, 59037 Lille, FranceSearch for more papers by this authorPierre Fenaux, Pierre Fenaux Service des Maladies du Sang, C.H.U., 1 Place de Verdun, 59037 Lille, FranceSearch for more papers by this author First published: November 1992 https://doi.org/10.1111/j.1365-2141.1992.tb06480.xCitations: 17AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume82, Issue3November 1992Pages 623-626 RelatedInformation

Secondary leukemias are a major complication of chemotherapy and/or radiotherapy administered in patients with malignant or non malignant disorders. They are usually preceded by a phase of myelodysplastic syndrome (MDS). Most of these secondary leukemias and MDS are associated with clonal chromosome abnormalities which frequently include partial deletions or complete loss of chromosome 7. The latter cytogenetic aberrations are also frequently encountered in de novo acute nonlymphocytic leukemia [1].

In a previous report we found point mutations in exons 5-8 of the P53 gene in five of 46 patients with acute myeloid leukaemia (AML), with a predominance of mutations in the 10 patients with 17p monosomy. In this report we extended our findings studying such mutations in 66 unselected additional cases of AML, using polymerase chain reaction single strand conformation polymorphism (SSCP) analysis and nucleotide sequencing. Three of the 66 new cases had a point mutation, leading to a change in one encoded amino acid. Thus, eight of the 112 AML studied had P53 mutations in exons 5-8, suggesting that the incidence of P53 mutation is relatively low in AML. A predominance of mutations in exon 8 (5/8) was found. Six of the eight patients with mutations were older than 60 years of age, and all eight cases had a short survival. All seven mutated cases karyotyped showed complex cytogenetic findings, especially monosomy 5 and/or 7, thus questioning the pathogenic importance of P53 mutations in a context of multiple genetic abnormalities. However, five of them also had 17p monosomy, and in the remaining two cases SSCP and sequence analysis also suggested loss of the normal P53 allele. This supported a role for the P53 gene mutations in leukaemogenesis in the relatively small number of AML patients in whom they were found, through loss of tumour suppressive activity of both normal P53 alleles, as reported in solid tumours.

A new case of acute monocytic leukemia observed in a 73-year-old male (ANLLM5) with an unusual t(8;22)(p11;q13) is reported. The blasts did not demonstrate erythrophagocytosis, but the presence of both naphtol-ASD-chloro-acetate esterase and butyrate esterase activities was similar to that seen in cases with t(8;16)(p11;p13).Involvement of the 8p11 region in ANLLM4 and M5 is discussed, being the third most frequent rearrangement in acute leukemia with monocytic components seen at our Center.