alloHSCT

Allogeneic Hematopoietic Stem Cell Transplantation for ALL Patients with t(12;21)(p13;q22) Translocation

BONE MARROW TRANSPLANTATION , , , ,

N.N. Mamaev1, E.V. Semenova1, N.V. Stancheva1, V.A. Katerina1, I.M. Barkhatov1, A.V. Evdokimov1, E.G. Boychenko2, T.L. Gindina1, V.M. Kravtsova1, L.S. Zubarovskaya1, B.V. Afanasyev1

1 R.M. Gorbacheva Memorial Institute of Children Oncology, Hematology and Transplantation under I.P. Pavlov State Medical University, Saint Petersburg, Russian Federation

2 1st Municipal Children’s Hospital, Saint Petersburg, Russian Federation

For citation: Mamaev N.N., Semenova E.V., Stancheva N.V., Katerina V.A., Barkhatov I.M., Evdokimov A.V., Boichenko E.G., Gindina T.L., Kravtsova V.M., Zubarovskaya L.S., Afanas’ev B.V. Allogeneic Hematopoietic Stem Cell Transplantation for ALL Patients with t(12;21)(p13;q22) Translocation. Klin. onkogematol. 2014; 7(3): 327–34 (In Russ.).

ABSTRACT

The results of allogeneic hematopoietic stem cell transplantation (alloHSCT) in 10 pediatric patients (4 boys, 6 girls at the age of 4 to 17 years, mean age is 9.8 years) with relapses of acute lymphoblastic leukemia (ALL) with TEL-AMLI fusion gene are presented. The first remission duration ranged from 20 to 70 months (mean duration 39.9 months). Transplantation was performed in 6 patients during the second (and further) remission, whereas 4 patients underwent transplantation during the relapse. Six patients received a graft from matched related (n = 3) or unrelated (n = 3) donors, haploidentical HSCT was performed in four other patients because there was no donor. Conditioning regimens were myeloablative in 8 cases and RIC (Reduced Intensity Conditioning) in 2 cases. Successful engrafting took place in 9 (90 %) of 10 patients. Additional haploidentical transplantation was performed in 1 case, when the transplant was rejected.

Monitoring of treatment was performed by means of serial testing of TEL-AMLI fusion gene expression level, of serial donor chimerism and the blast cell count in bone marrow and peripheral blood. The study demonstrated that four patients younger than 4 years had TEL-AML1 gene expression at all stages of their disease, including pre- and post-transplantation period. Due to it, even the donor chimerism and blast cell count in bone marrow and/or peripheral blood changed. On the contrary, in 3 more patients, TEL-AML1 gene expression levels were low before alloHSCT, being absent after HSCT.

In general, seven patients have been monitored for 178–2627 days (at the average of 870 days) including two patients with post-transplant relapses. At the same time, 3 patients died on days 20–263 after transplantation.

The observed difference in response to chemotherapy might be supposedly explained by involvement of not only hematopoietic, but also mesenchymal cells into the leukemic process (this fact was demonstrated for this group of patients by S. Shalapour et al., 2010). But this fact should be confirmed in further studies.

Keywords: ALL, t(12;21)(p13;q22) translocation, alloHSCT, molecular monitoring, difference in response to treatment.

Address correspondence to: nikmamaev524@gmail.com

Accepted: May 22, 2014

Read in PDF (RUS) pdficon

REFERENCES

  1. Romana S.P., Mauchauffe M., Le Coniat M. et al. The t(12;21) of acute lymphoblastic leukemia results in a tel-AML1 gene fusion. Blood 1995; 85: 3662–70.
  2. Shurtleff S.A., Buijs A., Behm F.G. et al. TEL/AML1 fusion resulting from a cryptic t(12;21) is the most common genetic lesion in pediatric ALL and defines a subgroup of patients with an excellent prognosis. Leukemia 1995; 9: 1985–9.
  3. McLeen T.W., Ringold S., Neuberg D. et al. TEL/AML-1 dimerizes and is associated with a favorable outcome in childhood acute lymphoblastic leukemia. Blood 1996; 88: 4252–8.
  4. Loh M.L., Rubnitz J.E. TEL/AML1-positive pediatric leukemia: prognostic significance and therapeutic approaches. Curr. Opin. Hematol. 2002; 9: 345–52.
  5. Pui C.H., Campana D., Evans W.E. Childhood acute lymphoblastic leukemia – current status and future perspectives. Lancet Oncol. 2001; 2: 597–607.
  6. Loh M.L., Goldwasser M.A., Silverman L.B. et al. Prospective analysis of TEL/AML1-positive patients treated on Dana-Faber Cancer Institute Consortium Protocol 95-01. Blood 2006; 107: 4508–13.
  7. Burmeister T., Gokbuget N., Schwartz S. et al. Clinical features and prognostic implications of TCF3-PBX1 and ETV6-RUNX1 in adult acute lymphoblastic leukemia. Haematologica 2010; 95: 241–6.
  8. Pui C.H., Pei D., Campana D. et al. Improved prognosis for older adolescents with acute lymphoblastic leukemia. J. Clin. Oncol. 2011; 29(4): 386–91.
  9. Seeger K., Adams H.P., Buchwald D. et al. TEL-AML 1 fusion transcript in relapsed childhood acute lymphoblastic leukemia: the Berlin-Frankfurt-Munster Study Group. Blood 1998; 91: 1716–22.
  10. Seeger K., Stackelberg A.V., Taube T. et al. Relapse of TEL-AML1- positive acute lymphoblastic leukemia in childhood: A matched-pair analysis. J. Clin. Oncol. 2001; 19: 3188–93.
  11. Shalapour S., Eckert C., Seeger K. et al. Leukemia-associated genetic aberrations in mesenchymal stem cells of children with acute lymphoblastic leukemia. J. Mol. Med. 2010; 88: 249–65.

Acute myeloid leukemias with t(7;21)(p22;q22) translocation, 5q- deletion, CD56 expression, and hemophagocytosis: case report and literature review

CLINICAL PRESENTATION, DIAGNOSIS, AND MANAGEMENT OF MYELOID MALIGNANCIES , , , ,

N.N. Mamayev1, T.L. Gindina1, E.G. Boychenko2, A.V. Gorbunova1, V.M. Kravtsova1, N.V. Stancheva1, P.V. Kozhokar1, O.V. Paina1, L.S. Zubarovskaya1, and B.V. Afanasyev1

1 R.M. Gorbacheva Institute of Pediatric Oncology, Hematology and Transplantology, I.P. Pavlov Saint Petersburg State Medical University, Saint Petersburg, Russian Federation

2 Children’s City Hospital #1, Saint Petersburg, Russian Federation

ABSTRACT

We present the clinical and laboratory data on a 13-year old patient with the recently described variant of CD56-positive acute myeloid leukemia with criptic t(7;21)(p22;q22) translocation involving rearrangements of RUNX1 and USP42 genes, 5q deletion, and hemophagocytosis. According to the literature, this rare recently described AML subvariant mostly occurs in males, is resistant to chemotherapy, and can be successfully treated using allogeneic hematopoietic stem cell transplantation.

Keywords: acute myeloid leukemia, t(7;21)(p22;q22), 5q-, CD56+, resistance to chemotherapy, erythrophagocytosis, alloHSCT.

Read in PDF (RUS)pdficon

REFERENCES

  1. Paulsson K., Bekassy A.N., Olofsson T. et al. A novel and cytogenetically cryptic t(7;21)(p22;q22) in acute myeloid leukemia results in fusion of RUNX1 with the ubiquting-specific protease gene USP42. Leukemia 2006; 20(2): 224–9.
  2. Hock A.K., Vigneron A.M., Carter S., Ludwig R.L., Vousden K.H. Regulation of p53 stability and function by the deubiquitinating enzyme USP42. EMBO J. 2011; 30(24): 4921–30.
  3. Foster N., Paulsson K., Sales M. et al. Molecular characterization of a recurrent, semi-cryptic RUBX1 translocation t(7;21) in myelodysplastic syndrome and acute myeloid leukemia. Br. J. Haematol. 2010; 148(6): 938–43.
  4. Giguere A., Hebert J. Microhomologies and topoisomerase II consensus sequences identified near the breakpoint junctions of the recurrent t(7;21)(p22;q22) translocation in acute myeloid leukemia. Gen. Chrom. Cancer 2011; 50(4): 228–38.
  5. Jeandidier E., Gervais C., Radford-Weiss I. et al. A cytogenetic study of 397 consecutive acute myeloid leukemia cases identified three with a t(7;21) associated with 5q abnormalities and exhibiting similar clinical and biological features, suggesting a new, rare acute myeloid leukemia entity. Cancer Genet. 2012; 205(7–8): 365–72.
  6. Panagopoulos J., Gorunova L., Brandel P. et al. Myeloid leukemia with t(7;21)(p22;q22) and 5q deletion. Onсol. Rep. 2013; 30(4): 1549–52.
  7. Gindina T., Barkhatov I., Boichenko E. et al. A new case of acute myeloid leukemia with semi-cryptic t(7;21)(p22;q22). Atlas Genet. Cytogenet. Oncol. Haematol. 2012; 16(9): 689–91.
  8. Park J.E., Park I.J., Lim Y.A. et al. Hemophagocytosis by leukemic blasts in B lymphoblastic leukemia with t(12;21)(p13;q22); TEL-AML1 (ETV6-RUNX1): a case report. Ann. Clin. Lab. Sci. 2013; 43(2): 186–9.