Sequential allogeneic transplantation and ruxolitinib maintenance for a synchronous <i>PCM1‐JAK2</i> positive myeloid sarcoma and acute B‐lymphoblastic leukemia

Rizzuto, Giuliana; Leoncin, Matteo; Imbergamo, Silvia; Taurino, Daniela; Micò, Maria Caterina; Tosi, Manuela; Michelato, Anna; Buklijas, Ksenija; Spinelli, Orietta; Lussana, Federico; Lessi, Federica; Pizzi, Marco; Bonaldi, Laura; Binotto, Gianni; Gurrieri, Carmela

doi:10.1002/ccr3.5212

Cited by 7 publications

(4 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As previously stated, MS was listed as an AML subtype by the World Health Organization (WHO) and considered as a specific presentation of many other myeloid neoplasms, including MDS, MPN, and CML ( 1 , 12 , 13 ). Recently, two cases were reported in which MS and acute lymphoblastic leukemia occurred simultaneously ( 14 , 15 ). MS’s complex association with other hematologic neoplasms has resulted in a lack of separate epidemiologic data.…”

Section: Discussionmentioning

confidence: 99%

Incidence, clinical characteristics, and prognostic nomograms for patients with myeloid sarcoma: A SEER-based study

Xing

Zhu

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

BackgroundMyeloid sarcoma (MS) is a rare hematological tumor that presents with extramedullary tumor masses comprising myeloid blasts. A controversial issue is whether MS involving normal hematopoietic sites (liver, spleen, and lymph nodes) should be excluded in future studies. We aimed to compare MS characteristics and outcomes involving hematopoietic and non-hematopoietic sites and construct a prognostic nomogram exclusively for the latter.MethodsData from patients diagnosed with MS between 2000 and 2018 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. According to the primary site, patients were classified as having MS involving hematopoietic sites (hMS) or non-hematopoietic sites (eMS). Clinical characteristics and survival outcomes were compared between the two groups using Wilcoxon, chi-square, and log-rank tests. Cox regression analysis was used to identify eMS prognostic factors to establish prognostic nomograms. The models’ efficiency and value were assessed using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA).ResultsIn total, 694 patients were enrolled, including 86 with hMS and 608 with eMS. There were no sex, race or marital status distribution differences between the two groups. Patients with eMS had better overall and cancer-specific survival rates than those with hMS. Additionally, prognostic factor effects differed between the two groups. Patients with eMS were randomly divided into the training (number of patiens, n=425) and validation cohorts (n=183). Age, first primary tumor, primary site, and chemotherapy were used to establish nomograms. The C-index values of overall survival (OS) and cancer-specific survival (CSS) nomograms were 0.733 (validation: 0.728) and 0.722 (validation: 0.717), respectively. Moreover, ROC, calibration curves, and DCA confirmed our models’ good discrimination and calibration ability and potential clinical utility value.ConclusionOur study described the differences between patients with eMS and those with hMS. Moreover, we developed novel nomograms based on clinical and therapeutic factors to predict patients with eMS’ 1-, 3- and 5-year survival rates.

show abstract

Section: Discussionmentioning

confidence: 99%

Incidence, clinical characteristics, and prognostic nomograms for patients with myeloid sarcoma: A SEER-based study

Xing

Zhu

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…Ruxolitinib is the only JAK inhibitor known to be undergoing clinical assessment in an ALL setting. High clinical effectiveness of ruxolitinib in combination with multi-agent chemotherapy has been reported in only small number of patients with either CRLF2 r/ JAK -mutant or JAK2 r ALL ( Schrappe et al, 2012 ; Roberts et al, 2014a ; Schwab et al, 2016 ; Mayfield et al, 2017 ; Ding et al, 2018 ; Chen X. et al, 2019 ; Chen et al, 2022 ; Rizzuto et al, 2022 ). A phase 2 clinical trial (NCT02723994) led by the Children’s Oncology Group is currently assessing ruxolitinib in combination with chemotherapy for the treatment of ALL patients harboring CRLF2 and/or JAK pathway alterations ( Senkevitch and Durum, 2017 ).…”

Section: Progress Of Targeted Therapies For Jak2 -...mentioning

confidence: 99%

“…Furthermore, the use of ruxolitinib as a first-line therapy for MF has revealed several clinical limitations (also apparent with a subsequently approved JAK inhibitor fedratinib), which are directly relevant to ALL and are discussed in detail below. There have been few case reports to date documenting successful responses to ruxolitinib in Ph-like ALL, with only one report in JAK2 -mutant Ph-like ALL ( Mayfield et al, 2017 ) and four reports in JAK2 r Ph-like ALL ( Ding et al, 2018 ; Chen X. et al, 2019 ; Chen et al, 2022 ; Rizzuto et al, 2022 ). It is also difficult to decipher the role of graft-versus-leukemia effect in the context of allogeneic transplant and the “on-target” but “off-cancer” effects of ruxolitinib on the immune system.…”

Section: Introductionmentioning

confidence: 99%

JAK2 Alterations in Acute Lymphoblastic Leukemia: Molecular Insights for Superior Precision Medicine Strategies

Downes

McClure

McDougal

et al. 2022

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer, arising from immature lymphocytes that show uncontrolled proliferation and arrested differentiation. Genomic alterations affecting Janus kinase 2 (JAK2) correlate with some of the poorest outcomes within the Philadelphia-like subtype of ALL. Given the success of kinase inhibitors in the treatment of chronic myeloid leukemia, the discovery of activating JAK2 point mutations and JAK2 fusion genes in ALL, was a breakthrough for potential targeted therapies. However, the molecular mechanisms by which these alterations activate JAK2 and promote downstream signaling is poorly understood. Furthermore, as clinical data regarding the limitations of approved JAK inhibitors in myeloproliferative disorders matures, there is a growing awareness of the need for alternative precision medicine approaches for specific JAK2 lesions. This review focuses on the molecular mechanisms behind ALL-associated JAK2 mutations and JAK2 fusion genes, known and potential causes of JAK-inhibitor resistance, and how JAK2 alterations could be targeted using alternative and novel rationally designed therapies to guide precision medicine approaches for these high-risk subtypes of ALL.

show abstract

“…In terms of MLN-Eo with Haematologica | 108 December 2023 t(8;9)(p22;p24)/PCM1::JAK2 rearrangement and synchronous MS, only three cases have been reported to date (Table 1). [5][6][7] The treatment was unknown in one case and the other two cases were treated with local radiotherapy and chemotherapy. One of them then received allogenetic stem cell transplantation (ASCT), and the other was awaiting transplantation.…”

mentioning

confidence: 99%

Myeloid/lymphoid neoplasms associated with eosinophilia and rearrangements of <i>PCM1::JAK2</i> with erythroblastic sarcoma: a case report and literature review

Zhang

Zhu

et al. 2023

haematol

View full text Add to dashboard Cite

show abstract

Sequential allogeneic transplantation and ruxolitinib maintenance for a synchronous PCM1‐JAK2 positive myeloid sarcoma and acute B‐lymphoblastic leukemia

Cited by 7 publications

References 9 publications

Incidence, clinical characteristics, and prognostic nomograms for patients with myeloid sarcoma: A SEER-based study

Incidence, clinical characteristics, and prognostic nomograms for patients with myeloid sarcoma: A SEER-based study

JAK2 Alterations in Acute Lymphoblastic Leukemia: Molecular Insights for Superior Precision Medicine Strategies

Myeloid/lymphoid neoplasms associated with eosinophilia and rearrangements of <i>PCM1::JAK2</i> with erythroblastic sarcoma: a case report and literature review

Contact Info

Product

Resources

About