Allogeneic stem cell transplantation reverses the poor prognosis of CML patients with deletions in derivative chromosome 9

Lundán, Tuija; Volin, Liisa; Ruutu, Tapani; Knuutila, Sakari; Porkka, Kimmo

doi:10.1038/sj.leu.2403570

Cited by 4 publications

(1 citation statement)

References 7 publications

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“…The region is gene rich, contains 44 known genes and another 40 predicted genes based on genome sequence analysis [16]. Der(9) deletions were associated with a poor prognosis, including a responsiveness to hydroxyurea and interferon (IFN)-α therapy, and a possible negative impact following bone marrow transplantation [6,17]. Imatinib mesylate is a specific BCR/ABL tyrosine kinase inhibitor with significant clinical activity in patients with CML.…”

Section: Discussionmentioning

confidence: 99%

The Negative Prognostic Impact of Derivative 9 Deletions in Patients Who Received Hydroxyurea Treatment for Chronic Myelogenous Leukemia in the Chronic Phase

Li¹,

Xu²,

Wu³

et al. 2008

Oncol Res Treat

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Background: Chronic myeloid leukemia (CML) is characterized by the formation of the BCR/ABL fusion gene, as a consequence of the Philadelphia (Ph) translocation between chromosomes 9 and 22. This study was to investigate the incidence and prognostic significance of derivative chromosome 9 (der(9)) deletions in CML patients who received hydroxyurea treatment in the chronic phase. Patients and Methods: Fluorescence in situ hybridization (FISH) analysis was used to assess the der(9) deletion status of 48 CML patients in blast crisis (CMLBC). Results: Among the 48 CML patients, 8 (16.7%) showed der(9) deletions, and the deletions were also existent at diagnosis. The median duration of the chronic phase for patients with der(9) deletions was 18 (range 4–38) months compared to 48 (range 0–204) months for patients without deletions (p < 0.001). Der(9) deletions were not associated with increased karyotypic instability. There was no difference in the probability of the der(9) deletions between the cases having progressed to myeloid or lymphoid blast crisis. Conclusion: The results indicated that the FISH technique could effectively detect der(9) deletions. CML patients with der(9) deletions show more rapid progression and poorer prognosis, and the deletion status is a powerful prognostic factor.

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Section: Discussionmentioning

confidence: 99%

The Negative Prognostic Impact of Derivative 9 Deletions in Patients Who Received Hydroxyurea Treatment for Chronic Myelogenous Leukemia in the Chronic Phase

Li¹,

Xu²,

Wu³

et al. 2008

Oncol Res Treat

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Role of Allogeneic Stem Cell Transplantation for Adult Chronic Myeloid Leukemia in the Imatinib Era

Grigg

Hughes

2006

Biology of Blood and Marrow Transplantation

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Due to superior survival in the short to medium term, the first-generation ABL kinase inhibitor imatinib mesylate has generally supplanted all other therapies as the initial treatment of choice in chronic phase chronic myeloid leukemia. The role of allogeneic stem cell transplantation (alloSCT) has shifted from a preferred first-line therapy to a possible second- or third-line therapy. However, despite generally excellent responses to imatinib, some patients respond poorly or lose response, and the risk-benefit equation in these cases may rapidly shift in favor of the alloSCT option. These patients need to be identified as soon as possible so that the alloSCT option can be applied while they are still in controlled chronic phase. Monitoring of imatinib response in patients who have suitable donors and are potentially eligible for alloSCT needs to be frequent, sensitive, and accurate. Clear criteria for switching from imatinib therapy to the alloSCT option should be established for each patient according to the specific risk profile of the transplant. The potential efficacy and safety of clinical trials combining reduced intensity alloSCT with ABL kinase inhibitor therapy warrants further consideration.

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Fluorescentin situhybridization in the diagnosis, prognosis, and treatment monitoring of chronic myeloid leukemia

Landstrom

Tefferi

2006

Leukemia & Lymphoma

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The unique molecular characteristic of chronic myeloid leukemia (CML), the disease-causing ABL (9q34) to BCR (22q11) translocation, has provided an invaluable tool for disease diagnosis and monitoring of treatment response. The traditional standard in this regard is bone marrow karyotype, also known as conventional cytogenetics (CC), which reveals a shortened chromosome 22, the Philadelphia chromosome, t(9;22)(q34;q11). CC in CML has also been effectively used for monitoring the response to drug therapy. However, this particular laboratory test misses submicroscopic BCR/ABL translocations and is suboptimal for minimal residual disease (MRD) assessment. Both fluorescence in situ hybridization (FISH) and reverse-transcriptase polymerase chain reaction (RT-PCR) feature higher sensitivity in terms of both diagnosis and MRD assessment in CML, compared to CC. Another advantage of these alternative tests is their effective applicability to peripheral blood specimens. The current review highlights the practical literature with respect to the use of FISH for CML whereas the use of RT-PCR has been extensively covered in recent communications.

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Allogeneic stem cell transplantation reverses the poor prognosis of CML patients with deletions in derivative chromosome 9

Cited by 4 publications

References 7 publications

The Negative Prognostic Impact of Derivative 9 Deletions in Patients Who Received Hydroxyurea Treatment for Chronic Myelogenous Leukemia in the Chronic Phase

The Negative Prognostic Impact of Derivative 9 Deletions in Patients Who Received Hydroxyurea Treatment for Chronic Myelogenous Leukemia in the Chronic Phase

Role of Allogeneic Stem Cell Transplantation for Adult Chronic Myeloid Leukemia in the Imatinib Era

Fluorescentin situhybridization in the diagnosis, prognosis, and treatment monitoring of chronic myeloid leukemia

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