Infectious complications after intensive chemotherapy with CLAG-M versus 7+3 for AML and other high-grade myeloid neoplasms

Walti, Carla S; Halpern, Anna B.; Kiem, Erika S.; Chung, E. Lisa; Schonhoff, Kelda; Huebner, Emily M.; Delaney, Colleen; Liu, Catherine; Pergam, Steven A.; Cheng, Guang Shing; Kimball, Louise E.; Leisenring, Wendy; Boeckh, Michael; Walter, Roland B.; Hill, Joshua A.

doi:10.1038/s41375-022-01786-9

Cited by 6 publications

(7 citation statements)

References 37 publications

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“…The duration of neutropenia for CLAG-M/CLAG has previously been reported by this study group, with a median time to neutrophil recovery >500 cells per μL of 26 and 30 days, respectively. 3 , 8 This is considerably longer that what is reported for more traditional AML regimens 18 and is a key risk factor for IFD. 19 …”

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confidence: 84%

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Invasive fungal infections after CLAG-M/CLAG chemotherapy for acute myeloid leukemia and high-grade myeloid neoplasms

et al. 2023

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CLAG-M (cladribine, high-dose cytarabine [HiDAC], G-CSF, mitoxantrone)/CLAG are contemporary intensive chemotherapy regimens associated with higher and deeper complete remission rates than 7+3 (cytarabine, anthracycline)/HiDAC, but with greater myelosuppression and potential infection risks. Here, we compared the cumulative incidence (CI) and patterns of invasive fungal disease (IFD) between these regimens by identifying proven/probable and possible cases of IFD following CLAG-M (n=332) and 7+3 (n=115) chemotherapy and subsequent treatment cycles in adults ≥18 years old with newly diagnosed (ND) or relapsed/refractory (R/R) AML or other high-grade myeloid neoplasms between 2006 and 2018. By 90 days (D90) after initiating treatment, the CI of proven/probable IFD was 20% with CLAG-M and 12% with 7+3 (p=0.17). There was no significant difference in the CI of IFD between ND CLAG-M and R/R CLAG-M. Without mold-active prophylaxis, the D90 CI of proven/probable IFD was significantly higher in the CLAG-M than the 7+3 cohort (28% versus 11%; p=0.007), but this difference was mitigated with mold-active prophylaxis (CLAG-M, 7.5%; 7+3, 0%; p=0.65). After each chemotherapy treatment cycle, the CI of newly diagnosed IFD was similar, ranging from 15-20%. Use of mold-active prophylaxis was the only factor associated with reduced IFD risk in adjusted models (HR, 0.32; 95% confidence interval, 0.18-0.56). Together, these data indicate that the IFD risk with CLAG-M is higher than with 7+3 in the absence of mold-active prophylaxis; use of mold-active prophylaxis mitigates this risk.

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confidence: 84%

“… 3 , 4 , 5 , 6 , 7 However, because of the inclusion of cladribine and use of higher doses of cytarabine, CLAG-M is associated with increased myelosuppression, which may result in a higher risk of infection. 8 …”

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confidence: 99%

Invasive fungal infections after CLAG-M/CLAG chemotherapy for acute myeloid leukemia and high-grade myeloid neoplasms

et al. 2023

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“…We recently read the very interesting paper by Walti et al [ 1 ] in which they investigated infections occurred in Acute Myeloid Leukemia (AML) patients after induction chemotherapy. Between 2006 and 2018 they retrospectively collected data of newly diagnosed (ND) AML treated with cladribine, high dose cytarabine, G-CSF and dose escalated mitoxantrone (CLAG-M) or standard dose cytarabine plus anthracycline (7 + 3).…”

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confidence: 99%

Infectious complications after induction chemotherapy with FLAI(E) in newly diagnosed AML, omitting antibacterial prophylaxis

et al. 2023

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“…The median white blood cell count decreased to 0.11 (0.02-0.83) ×10 9 /L, and the median platelet decreased to 11 (3-16) ×10 9 /L. In patients achieving CR, the median time to neutrophil count >0.5×10 9 /L and time to platelet count >20×10 9 /L was 15 (13)(14)(15)(16)(17) days and 13 (13-18) days, respectively, from the start of chemotherapy.…”

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confidence: 99%

“…CLAG regimen can reach a CR rate of 61.7%, which is numerically higher than that with FLAG of 48.7%, however, there were no difference of overall survival between FLAG and CLAG (9). In recent years mitoxantrone added into CLAG (CLAG-M) was used to treat R/R AML and high-grade myeloid neoplasm, yielding a CR rate of 60%, and 1-year OS of 44% at most (14), however due to its strong myelosuppression, it presented a higher risk to infectious complications and invasive fungal infection, which was a primary or contributing cause of death in 59% patients (15,16). Therefore, new chemotherapy combinations should be designed and verified for R/R AML.…”

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confidence: 99%

Effectiveness of chemotherapy using bortezomib combined with homoharringtonine and cytarabine in refractory or relapsed acute myeloid leukemia: a phase II, multicenter, prospective clinical trial

Zhang,

Gao,

Wang

et al. 2023

Front. Oncol.

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BackgroundRefractory/relapsed acute myeloid leukemia (R/R AML) has unsatisfactory outcomes even after allogeneic hematopoietic stem cell transplantation. Long-term survival is mainly influenced by complete remission (CR) rates after induction therapies.ObjectivesTo investigate CR/CR with incomplete hematologic recovery (CRi) rates and adverse events with a new induction therapy (bortezomib, homoharringtonine, and cytarabine [BHA]) for patients with R/R AML.MethodsWe enrolled 21 patients with R/R AML (median age, 42 [range, 30–62] years), who received BHA for remission induction (bortezomib, 1.3 mg/m2/day on days 1 and 4; homoharringtonine, 4 mg/m2/day for 5 days, and cytarabine, 1.5 g/m2/day for 5 days). CR and adverse events were assessed.ResultsAfter one course of BHA, the CR/CRi and partial remission rates were 38.1% and 14.3%, respectively, with an overall response rate (ORR) of 52.4% in 21 patients. 9 of 21 patients harbored FLT3-ITD or FLT3-TKD mutations, and achieved either CR/CRi or ORR of 66.7% (P=0.03) by comparison with that in R/R AML without FLT3 mutation. After induction therapy, consolidation chemotherapy or allogeneic hematopoietic stem cell transplantation led to a one-year overall survival of 27.8% in all patients. One-year relapse-free survival was 50% in 8 patients who had achieved CR/CRi after one course of BHA. During induction, non-hematologic adverse events (grade 3/4) commonly were infection (90.5%), hypokalemia (14.4%), hypocalcemia (14.3%), and mucositis (9.5%). In patients achieving CR, the median time to neutrophil count >0.5×109/L and time to platelet count >20×109/L were 15 (13–17) days and 13 (13–18) days, respectively.ConclusionBHA chemotherapy regimen was safe and tolerable to serve as an induction therapy for R/R AML, particularly with FLT3 mutation. The higher CR/CRi rate will give a clue to determine a potentialeffectiveness of BHA for AML patients carrying FLT3 mutation in a further investigation.Clinical trial registrationhttps://www.chictr.org.cn/, identifier ChiCTR2000029841.

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Infectious complications after intensive chemotherapy with CLAG-M versus 7+3 for AML and other high-grade myeloid neoplasms

Cited by 6 publications

References 37 publications

Invasive fungal infections after CLAG-M/CLAG chemotherapy for acute myeloid leukemia and high-grade myeloid neoplasms

Invasive fungal infections after CLAG-M/CLAG chemotherapy for acute myeloid leukemia and high-grade myeloid neoplasms

Infectious complications after induction chemotherapy with FLAI(E) in newly diagnosed AML, omitting antibacterial prophylaxis

Effectiveness of chemotherapy using bortezomib combined with homoharringtonine and cytarabine in refractory or relapsed acute myeloid leukemia: a phase II, multicenter, prospective clinical trial

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