Cytopenias after day 28 in allogeneic hematopoietic cell transplantation: impact of recipient/donor factors, transplant conditions and myelotoxic drugs

Nakamae, Hirohisa; Storer, Barry E.; Sandmaier, Brenda M.; Maloney, David G.; Davis, Chris; Corey, Lawrence; Storb, Rainer; Boeckh, Michael

doi:10.3324/haematol.2011.044966

Cited by 54 publications

(44 citation statements)

References 27 publications

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“…Engraftment was poor, and mycophenylate and trimethoprim-sulfamethoxazole, as well as other potentially myelosuppressive medications were administered [8]. Her spleen was not enlarged post-transplantation and she had no evidence for a microangiopathic process.…”

Section: Casementioning

confidence: 99%

Use of eltrombopag, a thrombopoietin receptor agonist, in post‐transplantation thrombocytopenia

et al. 2012

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using the STA-Compact instrument (Diagnostica Stago, Parsippany, NJ) was used to quantify anti-Factor Xa (LMWH) activity for enoxaparin. The sensitivity of this assay is 0.2 U/mL and within run imprecision is 5.5 (% CV) at 1 U/mL. The assay is linear between 0.2 and 2.0 U/mL. All anti-Factor Xa levels were analyzed by technicians blinded to the assigned treatment regimen. The target range for peak anti-Factor Xa levels was chosen to be 0.2-0.5 IU/mL [14].Statistical analyses.. The sample size for this pilot study was chosen to provide a cohort large enough to identify differences between groups, based on previous studies [17]. Descriptive statistics were used to calculate summary data. Data are represented as the mean ± SD, unless otherwise indicated. For all analyses, continuous variables were assessed for normality visually and with skewness and kurtosis tests (version 11.0, StataCorp, College Station, TX 77845). Parametric, two-tailed t-tests or ANOVA were used for continuous variables and the chi-square and Fisher's exact test for categorical variables with a predetermined alpha level of P < 0.05. Stepwise, multiple regression analyses were used to identify any pre-specified variables potentially affecting peak anti-Factor Xa levels, including age, actual body weight, BMI, time (enoxaparin dose administration to anti-Factor Xa measurements), gender, or estimated creatinine clearance. AcknowledgmentsAuthors thank all the patients that agreed to participate in this study, Ms. Pam Proctor and Linda Kelly for their research oversight, Dr. Chris Lehman for his assistance with anti-Factor Xa measurements, and Diana Lim for her assistance with illustrations and tables.

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Section: Casementioning

confidence: 99%

Use of eltrombopag, a thrombopoietin receptor agonist, in post‐transplantation thrombocytopenia

et al. 2012

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“…However, while NMA conditioning had protective effects on anemia and thrombocytopenia after day 28 there was no significant reduction of neutropenia either overall or in the context of ganciclovir use. 48 Elderly patients appear to be more prone to cumulative toxicities of post-HCT drug regimens, but NMA conditioning, optimized HLA matching, and higher doses of CD34 + cell infusions reduced the risk of cytopenia after day 28.…”

Section: Toxicities and Infectionsmentioning

confidence: 99%

Nonmyeloablative allogeneic hematopoietic cell transplantation

Storb

Sandmaier

2016

Haematologica

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“…87 Therefore, the lower NRM using RIC regimens appears to be driven not by less GvHD and late opportunistic infections, but by lower rates of acute complications, such as mucositis, idiopathic pneumonitis, sinusoidal obstruction syndrome, hemorrhagic cystitis, nephrotoxicity and early bacterial infections. 18,81,86,[88][89][90][91][92][93][94][95] Interestingly, the risk for secondary malignancies does not appear to be lower for RIC vs myeloablative transplants despite the lower doses of chemotherapy and radiation. 96 The differences in the toxicity profile impact the timing of complications.…”

Section: Toxicitymentioning

confidence: 99%

Reduced-intensity conditioned allogeneic SCT in adults with AML

Reshef

Porter

2015

Bone Marrow Transplant

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AML is currently the most common indication for reduced-intensity conditioned (RIC) allo-SCT. Reduced-intensity regimens allow a potent GVL response to occur with minimized treatment-related toxicity in patients of older age or with comorbidities that preclude the use of myeloablative conditioning. Whether RIC SCT is appropriate for younger and more standard risk patients is not well defined and the field is changing rapidly; a prospective randomized trial of myeloablative vs RIC (BMT-CTN 0901) was recently closed when early results indicated better outcomes for myeloablative regimens. However, detailed results are not available, and all patients in that study were eligible for myeloablative conditioning. RIC transplants will likely remain the standard of care as many patients with AML are not eligible for myeloablative conditioning. Recent publication of mature results from retrospective and prospective cohorts provide contemporary efficacy and toxicity data for these attenuated regimens. In addition, recent studies explore the use of alternative donors, introduce regimens that attempt to reduce toxicity without reducing intensity, and identify predictive factors that pave the way to personalized approaches. These studies paint a picture of the future of RIC transplants. Here we review the current status of RIC allogeneic SCT in AML. ( Bone Marrow Transplantation THE RATIONALE FOR RIC IN AMLTraditional myeloablative transplants are effective in part due to a potent immunologic GVL effect independent of the conditioning regimen. The GVL response has been repeatedly demonstrated in allo-SCT 1,2 and through the use of DLI. 3,4 The ability to harness GVL yet minimize toxicity is highly relevant in AML, which is common in older patients and often incurable with chemotherapy alone. In 2013, AML was the most common indication for allo-SCT, 35% of AML transplants were in patients over age 60 and over 40% were performed with reduced-intensity conditioning (RIC) regimens (data from CIBMTR-Center for International Blood and Marrow Transplant Research).Data from animal models 5,6 and clinical observations regarding GVL activity [1][2][3][4]7 facilitated the development of RIC regimens. The success of initial attempts to use low-dose (2 Gy) TBI alone as conditioning was hindered by frequent graft rejections. The addition of fludarabine to low-dose TBI promoted engraftment with encouraging outcomes. [8][9][10][11][12] This supported a conceptual shift in allo-SCT away from dose intensity toward less myelotoxic regimens that rely on a potent GVL response. EFFICACY-IS THERE AN IDEAL CONDITIONING REGIMEN?The definition of RIC has been a moving target. The term 'reduced intensity' describes regimens characterized by lower rates of toxicities compared with myeloablative transplants. RIC regimens can be further classified as non-myeloablative when they result in minimal cytopenias. These regimens presumably have minimal or no direct effect on leukemic cells, relying solely on the GVL response. 13 The CIBMTR defines a RIC regimen ...

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Cytopenias after day 28 in allogeneic hematopoietic cell transplantation: impact of recipient/donor factors, transplant conditions and myelotoxic drugs

Cited by 54 publications

References 27 publications

Use of eltrombopag, a thrombopoietin receptor agonist, in post‐transplantation thrombocytopenia

Use of eltrombopag, a thrombopoietin receptor agonist, in post‐transplantation thrombocytopenia

Nonmyeloablative allogeneic hematopoietic cell transplantation

Reduced-intensity conditioned allogeneic SCT in adults with AML

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