Nilotinib restores long-term full-donor chimerism in Ph-positive acute lymphoblastic leukemia relapsed after allogeneic transplantation

Merante, S.; Colombo, Anna; Calatroni, Silvia; Rocca, Barbara; Boni, Marina; Bernasconi, Paolo; Bonvini, L; Soverini, Simona; Alessandrino, Emilio Paolo

doi:10.1038/bmt.2009.6

Cited by 16 publications

(11 citation statements)

References 10 publications

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“…Unlike previous reports, our patient did not receive additional chemotherapy and/or donor lymphocyte infusions after relapse and went into molecular remission on single agent nilotinib, despite 70% blasts in a hyper-cellular marrow [12,13]. One month after starting nilotinib she reverted back to 100% donor reconstitution, without additional stem cells or lymphocytes.…”

Section: Discussioncontrasting

confidence: 54%

Persistent complete molecular remission after nilotinib and graft-versus-leukemia effect in an acute lymphoblastic leukemia patient with cytogenetic relapse after allogeneic stem cell transplantation

2012

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We report the successful treatment and sustained molecular remission using single agent nilotinib in a relapsed Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia patient after allogeneic hematopoietic stem cell transplantation. Compared to previously published studies, this is the first report where a patient did not receive additional chemotherapy after relapse, nor did she receive donor lymphocyte infusions. With nilotinib, the patient reverted back to normal blood counts and 100% donor reconstitution by single tandem repeat (STR) chimerism analysis in the bone marrow and in peripheral blood, granulocytes, T and B-lymphocytes. This report also highlights the use of nilotinib in combination with extracorporeal photopheresis (ECP) for concomitant graft-versus-host disease. Our data suggests that ECP, together with nilotinib, did not adversely affect the overall Graft-versus-leukemia (GVL) effect.

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Section: Discussioncontrasting

confidence: 54%

Persistent complete molecular remission after nilotinib and graft-versus-leukemia effect in an acute lymphoblastic leukemia patient with cytogenetic relapse after allogeneic stem cell transplantation

2012

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“…Recent studies have also shown that combining imatinib treatment with a donor lymphocyte infusion was effective in re-inducing a durable molecular remission in the case of relapsed Ph+ ALL [17]. With the documented efficacy of nilotinib for managing patients with relapsed Ph+ ALL after transplantation, the challenge has now shifted to maintaining these remissions (table 1) [18,19]. Interestingly, in the current case, nilotinib effectively controlled the MRD and induced durable molecular remission for extramedullary chloroma.…”

Section: Discussionmentioning

confidence: 99%

Pre-Emptive Treatment with Nilotinib after Second Allogeneic Transplantation in a Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Patient with High Risk of Relapse

Kang

Moon²,

Chae³

et al. 2010

Acta Haematol

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Although a tyrosine kinase inhibitor (TKI) targeted for BCR/ABL administered in combination with chemotherapy has been established as the current first-line strategy for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), relapse remains common, even among allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Recently, preclinical and preliminary clinical studies suggested a potential therapeutic role of nilotinib, a second-generation TKI, in Ph+ ALL, including patients who have undergone prior allo-HSCT. This report presents the case of a patient with a post-transplant persistent positive BCR/ABL value, who was treated with imatinib and dasatinib before a second allo-HSCT. The patient started taking nilotinib due to a persistent BCR/ABL value and residual mass in her ovaries after a second allo-HSCT. Nine months after introducing nilotinib, the patient achieved complete molecular remission, and despite the continued existence of the residual ovary mass, no hot spot was found in her positron emission tomography scan. The present paper also reviews existing literature on the pre-emptive use of nilotinib for Ph+ ALL patients who received all-HSCT.

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“…The rates for pleural or pericardial effusions and edema were low both in patients with early phase CML and patients with advanced phase CML [93, 94]. Preliminary data suggest that Nilotinib is well tolerated also in patients who have received an allogenic transplantation [101]. …”

Section: Rational For Using Tki In Cgvhdmentioning

confidence: 99%

Tirosin Kinase Inhibitors in Chronic Graft versus Host Disease: From Bench to Bedside

Olivieri

Coluzzi

Attolico

et al. 2011

The Scientific World JOURNAL

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Chronic Graft Versus Host Disease (cGVHD) is a major complication of allogeneic stem-cell transplantation (SCT). In many inflammatory fibrotic diseases, such as Systemic Scleroderma (SSc) and cGVHD with fibrotic features, an abnormal activation of transforming growth factor (TGFβ) and platelet-derived growth factor receptor (PDGF-R) pathways have been observed. Tyrosin Kinase Inhibitors (TKIs), which are currently used for treatment of patients with Chronic Myeloid Leukemia (CML), share potent antifibrotic and antiinflammatory properties, being powerful dual inhibitors of both PDGF-R and TGFβ pathways. Moreover accumulating in vitro data confirm that TKIs, interacting with the TCR and other signalling molecules, carry potent immunomodulatory effects, being involved in both T-cell and B-cell response. Translation to the clinical setting revealed that treatment with Imatinib can achieve encouraging responses in patients with autoimmune diseases and steroid-refractory cGVHD, showing a favourable toxicity profile. While the exact mechanisms leading to such efficacy are still under investigation, use of TKIs in the context of clinical trials should be promoted, aiming to evaluate the biological changes induced in vivo by TKIs and to assess the long term outcome of these patients. Second-generation TKIs, with more favourable toxicity profile are under evaluation in the same setting.

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Nilotinib restores long-term full-donor chimerism in Ph-positive acute lymphoblastic leukemia relapsed after allogeneic transplantation

Cited by 16 publications

References 10 publications

Persistent complete molecular remission after nilotinib and graft-versus-leukemia effect in an acute lymphoblastic leukemia patient with cytogenetic relapse after allogeneic stem cell transplantation

Persistent complete molecular remission after nilotinib and graft-versus-leukemia effect in an acute lymphoblastic leukemia patient with cytogenetic relapse after allogeneic stem cell transplantation

Pre-Emptive Treatment with Nilotinib after Second Allogeneic Transplantation in a Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Patient with High Risk of Relapse

Tirosin Kinase Inhibitors in Chronic Graft versus Host Disease: From Bench to Bedside

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