Allogeneic hematopoietic stem cell transplantation for refractory mycosis fungoides (MF) and Sezary syndrome (SS)

Atilla, Erden; Atilla, Pinar Ataca; Bozdağ, Sinem Civriz; Yüksel, Meltem Kurt; Toprak, Selami Koçak; Topçuoğlu, Pervin; Akay, Bengü Nisa; Şanlı, Hatice; Gürman, Günhan; Özcan, Muhıt

doi:10.1007/s12185-017-2245-x

Cited by 18 publications

(24 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Refractory MF and capability of progression to systemic MF may be related with innate or adaptive immune system during disease course. In fact, allogeneic hematopoietic stem cell transplantation [ 20 ] or immune check point inhibitor [ 21 ] is considered as effective treatment for refractory or relapsed MF. In particular, a patient with refractory cutaneous T-cell lymphoma had a chimeric cytotoxic T lymphocyte antigen (CTLA4)-CD28 fusion, and the blockade of this chimeric fusion using ipilimumab showed marked response without toxicities [ 22 , 23 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical outcomes and prognostic factors in patients with mycosis fungoides who underwent radiation therapy in a single institution

Jang

Kim

et al. 2018

Radiat Oncol J

View full text Add to dashboard Cite

PurposeWe aimed to evaluate clinical outcomes including progression-free survival (PFS), overall survival (OS), partial response, and complete response in patients who underwent radiation therapy (RT) for mycosis fungoides (MF). Also, we sought to find prognostic factors for clinical outcomes.Materials and MethodsTotal 19 patients confirmed with MF between 1999–2015 were retrospectively reviewed. Clinical and treatment characteristics, clinical outcomes, and and toxicities were analyzed.ResultsEleven patients were treated with total skin electron beam radiotherapy (TSEBT) and 8 patients with involved field radiation therapy (IFRT) with median dose of 30 Gy, respectively. The median time interval from diagnosis to RT was 2.6 months (range, 0.4 to 87.3 months). The overall response rate was 100%; 11 patients (57.9%) had a complete response and 8 patients (42.1%) a partial response. The presence of positive lymph node at the time of consultation of RT was associated with lower OS (p = 0.043). In multivariate analysis, PFS was significantly lower for patients with increased previous therapies experienced following RT (p = 0.019) and for patients showing PR during RT (p = 0.044). There were no reported grade 3 or more skin toxicities related with RT.ConclusionBoth IFRT and TSEBT are effective treatment for MF patients. Patients with short disease course before RT or complete response during RT are expected to have longer PFS. Positive lymph node status at the initiation of RT was associated woth poor OS, suggesting other treatment modalities such as low-dose RT for patients with low life-expectancy.

show abstract

Section: Discussionmentioning

confidence: 99%

Clinical outcomes and prognostic factors in patients with mycosis fungoides who underwent radiation therapy in a single institution

Jang

Kim

et al. 2018

Radiat Oncol J

View full text Add to dashboard Cite

show abstract

“…The malignant T cells show constitutive activation and propensity for T-helper 2 cytokine production [ 8 ] that suppresses cell-mediated immunity and increases infection risk [ 1 ]. Unfortunately, CTCL remains generally incurable except in rare cases of allogeneic stem cell transplantation [ 9 ]. Overall response rates to single agent systemic therapies, including the retinoid bexarotene, and histone deacetylase (HDAC) inhibitors vorinostat and romidepsin, range between 20–45% and relapses are not uncommon [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

BET inhibition in advanced cutaneous T cell lymphoma is synergistically potentiated by BCL2 inhibition or HDAC inhibition

et al. 2018

View full text Add to dashboard Cite

While several systemic therapies are approved for cutaneous T cell lymphoma (CTCL), a non-Hodgkin lymphoma of skin-homing T cells that may involve lymph nodes and peripheral blood in advanced stages, relapses are common. Mutational analysis of CTCL cells has revealed frequent amplification of the MYC oncogene, and bromodomain and extraterminal (BET) protein inhibitors have been shown to repress MYC expression in various malignancies. Towards a potential novel therapy, we thus sought to examine the effect of BET inhibition on CTCL cells in vitro. Each of the four tested BET inhibitors (JQ1, ABBV-075, I-BET762, CPI-0610) consistently induced dose-dependent decreases in viability of isolated patient-derived CTCL cells and established CTCL cell lines (MyLa, Sez4, HH, Hut78). This effect was synergistically potentiated by combination of BET inhibition with BCL2 inhibition (e.g. venetoclax) or histone deacetylase (HDAC) inhibition (e.g. vorinostat or romidepsin). There was also a marked increase in caspase 3/7 activation when JQ1 was combined with either vorinostat or romidepsin, confirming that the observed synergies are due in major part to induction of apoptosis. Furthermore, MYC and BCL2 expression were each synergistically repressed when CTCL cells were treated with JQ1 plus HDAC inhibitors, suggesting cooperative activities at the level of epigenetic regulation. Taken together, these data indicate that targeting BET proteins in CTCL represents a promising novel therapeutic strategy that may be substantially potentiated by combination with BCL2 or HDAC inhibition.

show abstract

“…Allogeneic hematopoietic stem cell transplantation may be a promising treatment for advanced MF and SS. 3 , 4 However, there is no established consensus on management after transplantation. A previous report showed that the rate of progression or relapse 1 year after transplantation was 50% and found that relapse is most common in the first year post-transplantation.…”

Section: Introductionmentioning

confidence: 99%

Long-term complete remission of early hematological relapse after discontinuation of immunosuppressants following allogeneic transplantation for Sezary syndrome

et al. 2018

View full text Add to dashboard Cite

Sezary syndrome (SS) is a leukemic form of cutaneous T-cell lymphoma and is chemo-resistant. Allogeneic hematopoietic stem cell transplantation is a promising therapy for SS; however, relapse is common. Therapeutic options after relapse have not been established. We managed an SS patient with hematological relapse within one month after transplantation. After discontinuation of immunosuppressants, she achieved complete remission and remained relapse-free. The chimeric analyses of Tcells showed that the full recipient type became complete donor chimera after immunological symptoms. This clinical course suggested that discontinuation of immunosuppressants may result in a graftversus- tumor effect, leading to the eradication of lymphoma cells.

show abstract

Allogeneic hematopoietic stem cell transplantation for refractory mycosis fungoides (MF) and Sezary syndrome (SS)

Cited by 18 publications

References 13 publications

Clinical outcomes and prognostic factors in patients with mycosis fungoides who underwent radiation therapy in a single institution

Clinical outcomes and prognostic factors in patients with mycosis fungoides who underwent radiation therapy in a single institution

BET inhibition in advanced cutaneous T cell lymphoma is synergistically potentiated by BCL2 inhibition or HDAC inhibition

Long-term complete remission of early hematological relapse after discontinuation of immunosuppressants following allogeneic transplantation for Sezary syndrome

Contact Info

Product

Resources

About