Impact of JAK2V617F-mutation status, allele burden and clearance after allogeneic stem cell transplantation for myelofibrosis
Haefaa Alchalby1, Anita Badbaran1, Tatjana Zabelina1, Guido Kobbe2, Joachim Hahn3, Daniel Wolff3, Martin Bornhäuser4, Christian Thiede4, Herrad Baurmann5, Wolfgang Bethge6, York Hildebrandt1, Ulrike Bacher1, Boris Fehse1, Axel R. Zander1 and Nicolaus Kröger1,*

Conclusion:

Depression is a common problem in oncology, with many possible causal factors, including disease progression, treatment-related toxicities, social issues, and fear about the possibility of death. Thus it is oftentimes difficult to ascertain a relationship between depression and drug exposure. However, a striking pattern emerges from this series of seven patients. All were coping well with their disease psychologically before imatinib/dasatinib therapy, yet developed profound depression during treatment, with many experiencing complete remission or improvement of symptoms after dose reduction or drug discontinuation. Three patients demonstrated significant suicidal ideation—a psychiatric emergency. Interestingly, two patients had relapse of depression after TKI rechallenge and one patient was randomly assigned to the treatment arm of a placebo-controlled trial.

 ABSTRACT 

Background: Tyrosine kinase inhibitors, such as imatinib, are not considered curative for chronic myeloid leukemia – regardless ofthe significant reduction of disease burden during treatment – since they do not affect the leukemic stem cells. However, the stochastic nature of hematopoiesis and recent clinical observations suggest that this view must be revisited.

Imatinib 800 mg Associated With Faster MMR vs Imatinib 400 mg or Imatinib 400 mg Plus Interferon in Previously Untreated Chronic-Phase CML.  June 11, 2010- German CML Study IV: randomized, treatment optimization trial......

Functional Activity of the OCT-1 Protein Is Predictive of Long-Term Outcome in Patients With Chronic-Phase Chronic Myeloid Leukemia Treated With Imatinib
J Clin Oncol. 2010 Apr 26; Epub ahead of print, DL White, P Dang, J Engler, A Frede, S Zrim, M Osborn, VA Saunders, PW Manley, TP Hughes

Abstract
Although tyrosine kinase inhibitors is effective for dramatically reducing CML cells, it might be difficult to eradicate completely the CML stem cells. We aimed to clarify the safety and effects of WT1 peptide vaccination in combination with imatinib therapy for a CML patient. A 51 year-old male with CML in CP, who showed a resistance against imatinib therapy for 2.5 years, began to be treated with 9mer modified-type WT1 peptides in combination with standard dose of imatinib. Although every 2-week-administration of WT1 peptides for 22 weeks did not show definite effects on the quantification of bcr-abl transcripts, by changing the administration from every 2 weeks to 4 weeks bcr-abl transcripts decreased remarkably. After 11 months of every 4-week-administration of the peptides and 12 months post cessation of the peptides bcr-abl transcripts achieved to the level below detection by RQ/RT-PCR (complete molecular response). WT1/MHC tetramer+CD8+ CTLs, which appeared after the second administration of WT1 peptides and remained more than 15 in number among 106 CD8+ T cells throughout the administration of WT1 peptides, are still present in the blood on 14th month post cessation of the peptides. An in vitro study as to the cytotoxicity of lymphocytes induced by mixed lymphocyte peptide culture demonstrated that cultured lymphocytes possessed cytotoxicity against WT1 expressing leukemia cells and the cytotoxicity was WT1-specific and MHC class I restricted. The present study showed that WT1 peptide vaccination in combination with TKI is feasible and effective in the therapy for imatinib-resistant CML.