Biomedical subjects

L Secker-Walker

Publications and source records attributed to L Secker-Walker.

6 recordsLinked to original sources

PubMed1998

FLAG-idarubicin and allogeneic stem cell transplantation for Ph-positive ALL beyond first remission.

We describe a single centre experience of eight consecutive patients with relapsed or refractory Ph+ ALL treated with the FLAG/idarubicin regimen followed by BMT or PBSCT. Following FLAG/idarubicin, one achieved a partial response and seven CR. All patients subsequently received allogeneic transplants: one sibling BMT, three matched unrelated (MUD) BMT and four sibling PBSCT. Two patients received second transplants with PBSC from their original BM donors following FLA/Ida with no further conditioning. Three patients are alive in CR 9, 24 and 32 months after transplant. Seven of eight patients had a cytogenetic response following FLAG/Ida induction and one of seven became bcr-abl negative. All eight patients had a complete cytogenetic response following transplant. Four of five assessable patients became p190 bcr-abl negative after transplant; three of these subsequently relapsed. Both patients with the p210 bcr-abl transcript remained bcr-abl positive in CR after transplant. FLAG/Ida was well tolerated and appears to be effective in inducing remission in relapsed Ph+ ALL. The use of FDR-containing chemotherapy without further conditioning prior to PBSCT deserves further study in heavily pre-treated patients and, in patients with relapsed ALL following BMT, may be a safer option than DLI (donor lymphocyte infusion) by avoiding the associated risk of aplasia.

Adolescent↗

PubMed1997

Severe aplastic anaemia in association with a unique constitutional translocation 46,XY,t(6;10)(q13;q22)c.

Severe aplastic anaemia (SAA) is an uncommon disorder which may be associated with several congenital syndromes. However, it has rarely been described in association with a constitutional karyotypic abnormality. The breakpoint of the balanced t(6:10)(q13:q22) translocation described here does not disrupt any currently recognized gene of haemopoietic or stromal importance. This report also highlights the problems inherent in the use of bone marrow transplantation (BMT) for treating multiply transfused aplastic anaemia patients.

Adolescent↗

PubMed1996

Cytogenetic findings in acute biphenotypic leukaemia.

We have studied the immunological and cytogenetic features of 26 patients with acute leukaemia classified as biphenotypic according to a scoring system based on the number and lineage specificity of antigens expressed on the blast cells. The series included 19 adults (age >15 years) and seven children. The cases were distributed in four immunophenotypic groups: (1)coexpression of myeloid and B antigens, 18 cases (69 percent);(2)myeloid and T cell antigens, six (23 percent); (3) one case with trilineage differentiation; and (4) one case with coexpression of both B and T cell antigens. Cytogenetic analysis revealed a normal karyotype in four cases (15 percent) and abnormal clones in 22 (85 percent). Eight patients had the Philadelphia (Ph) translocation, t(9;22)(q34;q11), (31 percent), three cases had structural aberrations of 6q and two had 11q23 rearrangements, one with t(11;19) and a second with t(4;11); the other eight cases had different alterations including t(9;12)(q1;q1), t(8;21)(q22;q22), t(2;7) (p1?3;q3?4), t(7;12)(q11;p11), hyperdiploidy and other structural abnormalities. The chromosomal rearrangements in children were characterised by abnormalities of 11q23 in two cases and the Ph translocation in three. Our data indicate that biphenotypic features are common in cases presenting with t(9;22) as the eight cases included here represent 47 percent of all cases of Ph+ve acute leukaemia studied in our Institution. Biphenotypic acute leukaemias comprise a heterogeneous group of leukaemias involving pluripotent stem cells. Cytogenetic studies are essential in characterising these cases as they will disclose several poor prognosis chromosome aberrations of which the Ph chromosome is the most frequent.

Adolescent↗

PubMed1994

Leukemia-associated changes identified by quantitative flow cytometry: I. CD10 expression.

We have compared CD10 antigen expression in normal fetal bone marrow with that of B-linage acute lymphoblastic leukemia (ALL). Both quantitative indirect immunofluoresence (QIFI) and direct immunofluorescence (IF) tests with Quantum beads were used to convert median fluorescence intensity (MFI) values into numbers of antigen molecules expressed per cell (AgE). Lymphoid precursors in the fetal marrow and liver expressed 3-12.5 x 10(3) CD10 molecules/cell with an upper limit of 5 x 10(4)/cell (MaxAgE). The median CD10 AgE in the different cases of acute B-lineage ALL were variable and ranged from undetectable to very high values (> 1.8 x 10(5). In 24 of the 72 cases (33%) tested with QIFI the median CD10 AgE was above the highest values seen in normal samples (> 5 x 10(4)/cell). An additional 23.6% of cases had higher median values than the normal median CD10 AgE. Next, CD10 antigen was quantitated in 78 cases during the routine multiparameter analysis of B-lineage leukemia using CD10/class II/CD34 3-color IF test or CD10/TdT 2-color IF test. The aberrant overexpression was confirmed in 43.6% of ALL cases. The CD10bright display suggested ALL diagnosis even when few cells were available for study, e.g., in early relapse and in ALL masquerading as aplastic anemia. The levels of CD10 expression were maintained in relapse. In addition, different CD10 levels were associated with the various chromosomal alterations: high CD10 levels (> 3 x 10(4)/cell) with hyperdiploidy, low CD10 levels (1.8-4 x 10(3)/cell) with the t(1;19) and undetectable levels (< 1.2 x 10(3)/cell) with the t(4;11) translocations.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers, Tumor↗

PubMed1987

Multiple chromosome abnormalities in a drug resistant TdT positive B-cell leukemia.

A 17-year old caucasian male presented with B-cell acute leukemia which proved aggressive and refractory to treatment. Cytogenic investigation showed a single clone with a complex karyotype 49,XY,del(2)(p13),+4,del(4)(p11),-6,+i(6)(p),+7,+8, t(8;14), (q24;q32),del(17)(p11). This includes the Burkitt's translocation and a deletion at the site of the immunoglobulin kappa light chain gene. Clonal evolution included tetraploidy, duplication of the derived chromosomes and, terminally, trisomy 1q. Immunological investigation revealed a monoclonal population of B-cell blasts, expressing the kappa light chain, and with an extremely rare combination of SIg and TdT positivity. Immunoglobulin gene rearrangement confirmed monoclonalility. Tetraploidy of the clone and del(17)(p11) have been previously described only in a cell line or at end stage disease in B-ALL. It is suggested that the chromosomal abnormalities present at diagnosis were directly related to the refractory nature of this leukemia.

Acute Disease↗

PubMed1987

Interleukin 2 enhances cytotoxic cell function in vitro after T-cell depleted marrow transplantation.

After T-cell depleted marrow transplantation, there is a rapid recovery of cytotoxic effector cells, with activity against targets not susceptible to killing by 'resting' natural killer cells. These targets include Epstein-Barr virus transformed B cells and leukaemic cell lines. Activated killer cell function declines by 3 months after transplantation. We find that when CD3 negative effector cells are obtained from these patients and cultured in vitro with interleukin 2 there is a further enhancement of cytotoxic activity against a range of target cells in the early post-transplant period, and a restoration of high level cytotoxic activity to effector cells obtained 3 months or more after the procedure. These results may have relevance to attempts to reduce the incidence of leukaemic relapse, and EBV + ve lymphoma outgrowth after T-cell depleted BMT.

Adolescent↗