Philadelphia chromosome as a recurrent event among therapy‐related acute leukemia

Aldoss, Ibrahim; Stiller, Tracey; Song, Joo Y.; Malki, Monzr M. Al; Ali, Haris; Salhotra, Amandeep; Aribi, Ahmed; Khaled, Samer K.; Gaytan, Popsie; Murata-Collins, Joyce; Palmer, Joycelynne; Snyder, David S.; O’Donnell, Margaret; Nakamura, Ryotaro; Stein, Anthony S.; Forman, Stephen J.; Marcucci, Guido; Pullarkat, Vinod

doi:10.1002/ajh.24604

Cited by 12 publications

(12 citation statements)

References 9 publications

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“…Ph chromosome is rarely observed among T-cell phenotype ALL and AML cases, and prior reports have shown that some of those cases were potentially therapy-related and developed after cytotoxic exposure. 6 , 19 Nonetheless, we have observed a trend toward higher rates of additional cytogenetic abnormalities among Ph + t-ALL compared to Ph + de novo ALL (73% vs . 50%, P =0.07), and this likely reflects various levels of genomic instability as a result of prior cytotoxic therapy.…”

Section: Discussionmentioning

confidence: 68%

Therapy-related acute lymphoblastic leukemia has distinct clinical and cytogenetic features compared to de novo acute lymphoblastic leukemia, but outcomes are comparable in transplanted patients

et al. 2018

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Therapy-related acute lymphoblastic leukemia remains poorly defined due to a lack of large data sets recognizing the defining characteristics of this entity. We reviewed all consecutive cases of adult acute lymphoblastic leukemia treated at our institution between 2000 and 2017 and identified therapy-related cases - defined as acute lymphoblastic leukemia preceded by prior exposure to cytotoxic chemotherapy and/or radiation. Of 1022 patients with acute lymphoblastic leukemia, 93 (9.1%) were classified as therapy-related. The median latency for therapy-related acute lymphoblastic leukemia onset was 6.8 years from original diagnosis, and this was shorter for patients carrying the MLL gene rearrangement compared to those with other cytogenetics. When compared to de novo acute lymphoblastic leukemia, therapy-related patients were older (P<0.01), more often female (P<0.01), and had more MLL gene rearrangement (P<0.0001) and chromosomes 5/7 aberrations (P=0.02). Although therapy-related acute lymphoblastic leukemia was associated with inferior 2-year overall survival compared to de novo cases (46.0% vs. 68.1%, P=0.001), prior exposure to cytotoxic therapy (therapy-related) did not independently impact survival in multivariate analysis (HR=1.32; 95% CI: 0.97–1.80, P=0.08). There was no survival difference (2-year = 53.4% vs. 58.9%, P=0.68) between the two groups in patients who received allogenic hematopoietic cell transplantation. In conclusion, therapy-related acute lymphoblastic leukemia represents a significant proportion of adult acute lymphoblastic leukemia diagnoses, and a subset of cases carry clinical and cytogenetic abnormalities similar to therapy-related myeloid neoplasms. Although survival of therapy-related acute lymphoblastic leukemia was inferior to de novo cases, allogeneic hematopoietic cell transplantation outcomes were comparable for the two entities.

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Section: Discussionmentioning

confidence: 68%

Therapy-related acute lymphoblastic leukemia has distinct clinical and cytogenetic features compared to de novo acute lymphoblastic leukemia, but outcomes are comparable in transplanted patients

et al. 2018

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“…In those patients positive for BCL-ABL1, the use of tyrosine kinase inhibitors has been used in combination with chemotherapy, although with the small number of cases, the effect of prognosis is not known [29,30].…”

Section: Discussionmentioning

confidence: 99%

Common B-cell acute lymphoblastic leukaemia in a 70-year-old woman presenting 2 years after carboplatin-taxane radiotherapy for endometrial cancer

Murray

Orrego

López

et al. 2019

ecancer

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Therapy-related acute lymphoblastic leukaemia (t-ALL) is a poorly defined entity and is not featured in the World Health Organization classification as a distinct clinical entity from acute lymphoblastic leukaemia (ALL), thus differing from therapy-related acute myeloid leukaemia and myelodysplasia. We present a case of tALL occurring 18 months after treatment for metastatic endometrial cancer with a regimen of carboplatin, paclitaxel and radiotherapy. The patient presented with severe pancytopenia and diagnosed with common-B ALL, and the cytogenetic analysis showed a previously unreported deletion in chromosome 19 (q13.1) in 100% of the blast cells. The patient declined further therapy and died 1 month later. This rare but serious side effect of chemo-radiotherapy should be considered when deciding on treatment options for gynaecological cancers.

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“…2 We recently performed differential mass-spectrometry analysis of urine proteins in SCA patients who did not have proteinuria and microalbuminuria, and found increased levels of orosomucoid (ORM) in the samples from patients with hemoglobinuria. 3 ORM is a major acute phase protein expressed in the liver and secreted into the circulation. Tissue injury, inflammation, infection, and cancer are associated with increased ORM expression and serum concentration.…”

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confidence: 99%

“…Samples were further separated into two groups: (i) samples with increased urinary hemoglobin (Hgb/CRE > 0.8 ng/mg, N 5 6) and (ii) samples with low urinary hemoglobin (Hgb/CRE < 0.45 ng/mg, N 5 14). 3 We conducted high resolution Our recent comparative proteomic analysis demonstrated increased levels of ORM in urine samples from SCA patient with Hgb/CRE > 0.8 ng/mg. 3 We selected three samples from a group with Hgb/CRE >0.8…”

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A retrospective survey of exposure history to chemotherapy or radiotherapy in 940 consecutive patients with primary myelofibrosis

et al. 2018

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Philadelphia chromosome as a recurrent event among therapy‐related acute leukemia

Cited by 12 publications

References 9 publications

Therapy-related acute lymphoblastic leukemia has distinct clinical and cytogenetic features compared to de novo acute lymphoblastic leukemia, but outcomes are comparable in transplanted patients

Therapy-related acute lymphoblastic leukemia has distinct clinical and cytogenetic features compared to de novo acute lymphoblastic leukemia, but outcomes are comparable in transplanted patients

Common B-cell acute lymphoblastic leukaemia in a 70-year-old woman presenting 2 years after carboplatin-taxane radiotherapy for endometrial cancer

A retrospective survey of exposure history to chemotherapy or radiotherapy in 940 consecutive patients with primary myelofibrosis

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