Moderate-dose cyclophosphamide for severe aplastic anemia has significant toxicity and does not prevent relapse and clonal evolution

Acquired severe aplastic anemia (SAA) is a rare hematologic disease associated with significant morbidity and mortality. Immune destruction of hemopoietic stem cells plays an important role in pathogenesis, as shown by successful treatment with immunosuppressive agents, leading to transfusion independence or complete recovery of peripheral blood counts in a proportion of patients. Growth factors can be combined with immunosuppressive therapy (IST) and may improve response rates, as recently shown with thrombopoietin analogs. Anabolic steroids may still play a role in combination with IST. The problem with IST is failure to respond and the development of late clonal disorders. Bone marrow transplantation (BMT) is the other therapeutic option: a matched sibling donor remains the best choice. For patients lacking a matched family donor, unrelated donors can be readily found, although mostly for patients of Caucasian origin. Other BMT options include unrelated cord blood or mismatched family donors. Acute and chronic graft-versus-host disease remain important complications of BMT. Patient age is a strong predictor of outcome for both IST and BMT, and must be considered when designing therapeutic strategies. Early diagnosis and treatment, as well as long-term monitoring, remain crucial steps for successful treatment of SAA.

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“…81 For these reasons, high-dose CY cannot be recommended as a nontransplant therapy outside a clinical trial.…”

Section: High-dose Cyclophosphamidementioning

confidence: 99%

How I treat acquired aplastic anemia

Bacigalupo

2017

Blood

324

267

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“…10 Specifically, very short telomere length in 3 or 4 of total lymphocytes, naïve T cells, memory T cells, and B cell subsets, as determined by Flow-FISH, is both highly sensitive and specific for DC. Whereas some patients have profoundly short telomeres, others may have telomere lengths that hover around the first percentile, as did the proband in Guo et al 1 Additionally, telomere length slightly below the first percentile across lymphocyte populations has been observed, albeit rarely, in patients with inherited bone marrow failure syndromes other than DC, such as Fanconi anemia, Diamond-Blackfan anemia, and Shwachman-Diamond syndrome.…”

mentioning

confidence: 77%

“…Ultimately, gene mutation data, as obtained by Guo et al, 1 can provide the essential support for an underlying telomere biology disorder. Thus, continuing efforts to arrive at the full repertoire of genes associated with the telomere biology disorders is of particular importance as we strive to accurately diagnose and provide optimal care to patients with BMF.…”

mentioning

confidence: 98%

Cyclophosphamide in severe aplastic anemia?

Latour

2014

Blood

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“…23 Moderate-dose (120 mg/kg) CY for untreated AA induced meaningful responses but showed significant toxicity in a study presented at the ASH annual meeting in 2012. 24 In view of its significant toxicity, the use of CY should be restricted 25 to clinical trials because less-toxic drugs are currently available.…”

Section: Treatment Options If There Is No Suitable Udmentioning

confidence: 99%

Management of the refractory aplastic anemia patient: what are the options?

Marsh

Kulasekararaj

2013

Blood

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Refractory aplastic anemia (AA) is defined as a lack of response to first-line immunosuppressive therapy (IST) with antithymocyte globulin and cyclosporin and is manifested as persistence of severe cytopenias at 6 months after IST. Although supportive care is critical for AA patients, it is of paramount importance for refractory disease in view of the longer duration of pancytopenia and susceptibility to life-threatening infections due to IST. Improvements in supportive care have largely contributed to better outcome over the past 2 decades, with 5-year overall survival reaching 57% during 2002 to 2008 for patients with AA unresponsive to initial IST. Exclusion of hypocellular myelodysplastic syndrome and constitutional BM failure masquerading as apparent idiopathic AA should be done in conjunction with centers of excellence. Hematopoietic stem cell transplantation is indicated if refractory AA patients are fit and have a suitably matched donor, either a sibling (>40-50 years) or unrelated donor. Patients lacking a fully matched donor should be considered for a second course of antithymocyte globulin plus cyclosporin, although response in the refractory setting is only ∼30% to 35%. Response may also occur with alemtuzumab or the thrombopoietin mimetic eltrombopag in refractory AA. The emerging data for alternate donor (cord or haploidentical) transplantation in AA has provided additional therapeutic choices to consider in refractory disease.

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Moderate-dose cyclophosphamide for severe aplastic anemia has significant toxicity and does not prevent relapse and clonal evolution

Abstract: Key Points Moderate-dose cyclophosphamide is associated with an unacceptable rate of toxicity in SAA, as in high-dose cyclophosphamide. Moderate-dose cyclophosphamide is an active regimen but is associated with a low response and does not prevent relapse or clonal evolution.

Cited by 38 publications

References 24 publications

How I treat acquired aplastic anemia

How I treat acquired aplastic anemia

Cyclophosphamide in severe aplastic anemia?

Management of the refractory aplastic anemia patient: what are the options?

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