Leukaemia relapse after allogeneic transplants for acute myeloid leukaemia: predictive role of <scp>WT</scp>1 expression

Pozzi, Sarah; Geroldi, Simona; Tedone, Elisabetta; Luchetti, Silvia; Grasso, Raffaella; Colombo, Nicoletta; Grazia, Carmen Di; Lamparelli, Teresa; Gualandi, Francesca; Ibatici, Adalberto; Bregante, Stefania; Lint, Maria Teresa Van; Raiola, Anna Maria; Dominietto, Alida; Varaldo, Riccardo; Signori, Alessio; Bacigalupo, Andrea

doi:10.1111/bjh.12181

Cited by 65 publications

(77 citation statements)

References 23 publications

(24 reference statements)

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“…14,15 In this view, pre-transplant MRD positive patients might receive prophylactic DLI to reduce relapse risk and improve survival. An additional possibility could be prophylactic treatment with hypomethylating agents, …”

Section: A B C Dmentioning

confidence: 99%

Combining flow cytometry and WT1 assessment improves the prognostic value of pre-transplant minimal residual disease in acute myeloid leukemia

et al. 2017

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Section: A B C Dmentioning

confidence: 99%

Combining flow cytometry and WT1 assessment improves the prognostic value of pre-transplant minimal residual disease in acute myeloid leukemia

et al. 2017

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“…Altered expression of WT1 in patients with ALL was associated with increased relapse [67]. In AML, increased WT1 expression correlated with increased disease burden, relapse, and poor overall survival [68][69][70][71]. While WT1 is also seen in healthy hematopoietic stem cells, anti-WT1 cytotoxic therapy did not result in adverse effects in this population [66].…”

Section: T Cells Targeting Leukemia-associated Antigensmentioning

confidence: 99%

Adoptive Immunotherapy for Leukemia with Ex Vivo Expanded T Cells

Russell¹,

Cruz²,

Bollard³

2015

CDT

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The development of novel T cell therapies to target leukemia has facilitated the translation of this approach for hematologic malignancies. Different methods of manufacturing leukemia-specific T cells have evolved, along with additional measures to increase the safety of this therapy. This is an overview of expanded T cell therapeutics with a focus on how the manufacturing strategies have been refined, and where the research is heading.

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“…До настоящего времени такой подход чаще ис-пользовался для диагностики минимальной оста-точной болезни после трансплантации гемопоэтиче-ских стволовых клеток (ТГСК) [1,4,[8][9][10][11][12][13][14][15][16][17][18][19][20][21][22], а также для раннего распознавания рецидивов ОЛ [4,9,[23][24][25][26][27][28][29]. В то же время исследований, посвященных оценке эффективности индукционных курсов химиотерапии, недостаточно [4,14,[30][31][32][33][34][35][36][37].…”

Section: Introductionunclassified

Efficacy of Chemotherapy in Acute Leukemia Patients Resistant to Previous Standard Treatment According to the Series Measurement of WT1 Gene Expression

Мамаев¹,

Gudozhnikova²,

Гиндина³

et al. 2018

Клиническая онкогематология

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Aim. To estimate the efficacy of chemotherapy in acute leukemia patients resistant to previous standard treatment according to the series measurement of WT1 expression. Materials & Methods. The series measurement of WT1 expression formed the basis of the efficacy estimation of induction chemotherapy in 31 patients (15 men and 16 women aged from 3 months to 68 years; the median age was 28 years) with prognostically unfavourable variants of acute myeloid (AML) and lymphoblastic leukemia (ALL) (23 AML and 8 ALL patients). The WT1 gene expression was measured at baseline and 2-3 weeks after the treatment by the quantitative real-time PCR. The threshold level for detection was 250 copies of WT1/104 copies of ABL. The cytogenetic profile of leukemia cells was assessed by standard cytogenetics and FISH. Results. The baseline expression level of WT1 varied from 305 to 58,569 copies/104 copies of ABL. The expected reduction of WT1 expression after the first induction chemotherapy treatment was reported in 22/23 (96 %) AML patients and in 6/8 (75 %) ALL patients. According to our results WT1 expression reached the threshold in 13/31 (42 %) patients, including 9 AML patients and 4 ALL patients. After 11/31 (35 %) patients received the second course of treatment, WT1 expression level became normal in 8 cases (5 ALL and 3 AML patients). Despite high dose chemotherapy, HSCT and such agents as blinatumomab and gemtuzumab, an unfavourable outcome was observed in 18/31 (58 %) patients including 6 patients with complex karyotype (CK+) and 2 patients with monosomal karyotype (MK+). Once the MK+ and CK+ combination was observed, in another case the MK+ was combined with the prognostically unfavourable inv(3)(q21q26) inversion. Conclusion. Our results show that the molecular monitoring should be included as part of treatment of the prognostically unfavourable acute leukemia. The WT1 gene was shown to be the most appropriate marker. WT1 expression was shown to correlate with the common fusion genes allowing to estimate the blast cell count at the molecular level.

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Leukaemia relapse after allogeneic transplants for acute myeloid leukaemia: predictive role of WT1 expression

Cited by 65 publications

References 23 publications

Combining flow cytometry and WT1 assessment improves the prognostic value of pre-transplant minimal residual disease in acute myeloid leukemia

Combining flow cytometry and WT1 assessment improves the prognostic value of pre-transplant minimal residual disease in acute myeloid leukemia

Adoptive Immunotherapy for Leukemia with Ex Vivo Expanded T Cells

Efficacy of Chemotherapy in Acute Leukemia Patients Resistant to Previous Standard Treatment According to the Series Measurement of WT1 Gene Expression

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