Fractionated total‐body irradiation preceding high‐dose cytosine arabinoside as a preparative regimen for bone marrow transplantation in children with acute leukemia

Kamani, Naynesh; Bayever, Eliel; August, Charles S.; Bunin, Nancy; Goldwein, Joel W.; D’Angio, Giulio J.

doi:10.1002/mpo.2950250304

Cited by 8 publications

(9 citation statements)

References 15 publications

(4 reference statements)

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“…1,3 In the setting of HSCT, the reported incidence of keratoconjunctivitis due to high-dose cytarabine in combination with TBI is 45-75%, although most reports have not mentioned the incidence of kerato-conjunctivitis, much less prophylactic measures against kerato-conjunctivitis. [4][5][6][7] In accordance with these reports, the results of our study indicated that the patients who received high-dose cytarabine and TBI frequently develop moderate to severe kerato-conjunctivitis (66%). Of note is that during highdose cytarabine therapy, all our patients received topical corticosteroid every 6 h, which has been reported to effectively prevent cytarabine-induced kerato-conjunctivitis.…”

Section: Discussionsupporting

confidence: 89%

“…1,3 In the setting of hematopoietic stem cell transplantation (HSCT), particularly in allogeneic HSCT, high-dose cytarabine is generally used in combination with TBI and/or other chemotherapeutic agents such as CY. [4][5][6][7][8][9] In contrast to a non-HSCT setting, this kerato-conjunctivitis has not been described as a clinically significant toxicity or has been disregarded as a minor toxicity in HSCT recipients. We have evaluated and reported the efficacy and safety of a conditioning regimen consisting of TBI and high-dose cytarabine for allogeneic HSCT.…”

Section: Introductionmentioning

confidence: 99%

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Reduced efficacy of topical corticosteroid in preventing cytarabine-induced kerato-conjunctivitis in patients receiving high-dose cytarabine and total body irradiation for allogeneic hematopoietic stem cell transplantation

Mori

Watanabe

Kurotori-Sotome

et al. 2008

Bone Marrow Transplant

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This study aimed to retrospectively evaluate the incidence of kerato-conjunctivitis in patients receiving TBI followed by high-dose cytarabine, and to clarify how effectively topical corticosteroid eye drops prevent kerato-conjunctivitis in these patients. Fifty-three patients who received cytarabine at a dose of 3 g/m 2 every 12 h for 4 days after receiving TBI (12 Gy) as a conditioning for allogeneic hematopoietic stem cell transplantation (HSCT) were evaluated. For the prophylaxis of kerato-conjunctivitis, all patients received betamethasone sodium phosphate eye drops every 6 h, starting 1 day before the first dose of cytarabine and continuing until 1 day after the last dose of cytarabine or the complete resolution of ocular symptoms. For grading of kerato-conjuncitivitis, the National Cancer Institute-Common Toxicity Criteria were used. Among the 53 patients, the grades of kerato-conjunctivitis were grade 0 in 13 patients, grade 1 in 6 patients (11.3%), grade 2 in 10 patients (18.9%) and grade 3 in 25 patients (47.2%). These results strongly suggest that topical corticosteroid eye drops could not effectively prevent the development of cytarabine-induced kerato-conjunctivitis in HSCT recipients who receive high-dose cytarabine following TBI. Further investigation into a more effective prophylaxis for cytarabine-induced kerato-conjunctivitis in this setting is required.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Reduced efficacy of topical corticosteroid in preventing cytarabine-induced kerato-conjunctivitis in patients receiving high-dose cytarabine and total body irradiation for allogeneic hematopoietic stem cell transplantation

Mori

Watanabe

Kurotori-Sotome

et al. 2008

Bone Marrow Transplant

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“…5 Ara-C/TBI regimens have also been evaluated, and reported outcomes were similar to those obtained with the CY/TBI regimen. [22][23][24] In some reports comparing HDAC/TBI regimens with CY/TBI regimens, no advantage in using the HDAC/TBI regimens was demonstrated, 25,26 while other reports showed that the HDAC/TBI regimens were more toxic. 27 Some investigators reported that HDAC-containing regimens were highly effective in reducing relapse rate after BMT.…”

Section: Discussionmentioning

confidence: 99%

Addition of high-dose Ara-C to the BMT conditioning regimen reduces leukemia relapse without an increase in toxicity

Mineishi

Atkinson

et al. 1999

Bone Marrow Transplant

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Summary:The optimal conditioning regimen for allogeneic BMT for hematological malignancies is still to be determined. We used a conditioning regimen including high-dose Ara-C (HDAC)/CY/TBI for patients at high risk for leukemic relapse (regimen A, Ara-C 3 g/m 2 every 12 h for six doses followed by CY 45 mg/kg for 2 days and TBI 13.2 Gy in eight fractions) and a standard CY/TBI conditioning regimen for patients at low risk (regimen B, CY 60 mg/kg for 2 days and TBI 13.2 Gy in eight fractions). We analyzed 55 patients treated with regimen A (group A) and 36 patients with regimen B (group B). Relapse rates (10.9% in group A, 2.9% in group B, P = 0.23), 5-year overall (53.2% in group A and 60.8% in group B, P = 0.26) and disease-free (47.7% in group A and 60.8% in group B, P = 0.11) survival rates were not significantly different between these groups, although group A consisted of high-risk patients. Regimen-related toxicities were not significantly different between the two groups. This result suggests that adding HDAC to CY/TBI conditioning regimen may reduce leukemic relapse and improve survival without increasing regimen-related toxicities. Keywords: allogeneic BMT; conditioning; toxicity; Ara-C; relapse Allogeneic BMT has been used effectively to treat a variety of hematologic malignancies. 1 Particularly for CML or myelodysplastic syndromes (MDS), it represents the only curative treatment modality. The combination of high-dose CY and TBI has been considered as a standard conditioning regimen for allogeneic BMT. 2,3 A variety of different conditioning regimens are currently being used including those which contain high-dose Ara-C (HDAC) 4 or high-dose etoposide. 5 mens, 6-8 but no study so far has shown a significant advantage of other regimens over CY/TBI.At the University of Wisconsin-Madison, we have used the standard conditioning regimen of CY/TBI for patients at low risk for leukemic relapse after BMT, and an intensified conditioning regimen of HDAC/CY/TBI for patients at higher risk, based on the hypothesis that the increased antitumor activity of HDAC would decrease the expected high incidence of leukemic relapse in patients with poor prognostic factors. In this article we summarize a prospective comparison of results obtained with these two regimens. Patients and methodsAll patients who underwent matched related allogeneic bone marrow transplantation at the University of Wisconsin-Madison between February 1990 and March 1997 with the diagnosis of AML, ALL, CML or MDS were entered in this study. Patients were assigned to a regimen according to their risk for leukemic relapse after BMT. Patients with the following diagnosis were considered to be at higher risk for leukemic relapse:(1) AML/MDS: second or subsequent complete remission (CR); first or subsequent relapse; primary refractory AML; high-risk cytogenetic features including deletions of chromosome 5 or 7 (Ϫ5, Ϫ7) or multiple cytogenetic abnormalities; preceding MDS, persistent cytogenetic abnormalities, or with central nervous system (CNS) involve...

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“…The results of this study indicated that mouth rinse during and shortly after high-dose cytarabine infusion is an effective and inexpensive measure to reduce the incidence of moderate to severe (particularly severe) oral mucositis in patients receiving high-dose cytarabinecontaining intensive regimen for allogeneic HSCT. Although the incidence of oral mucositis varies among the conditioning regimens, the regimen consisting of high-dose cytarabine and TBI has been known to cause oral mucositis at a high incidence (65-100%) [2][3][4][5][6]. Mouth rinse or mouth wash is generally recommended as a care in patients with oral mucositis to reduce the risk of mucositis-associated infection [9].…”

Section: Discussionmentioning

confidence: 99%

“…Cytarabine is one of the chemotherapeutic agents used in conditioning regimens for HSCT. In combination with TBI, high-dose cytarabine causes oral mucositis in about 65-100% of patients [2][3][4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Efficacy of mouth rinse in preventing oral mucositis in patients receiving high-dose cytarabine for allogeneic hematopoietic stem cell transplantation

et al. 2008

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High-dose cytarabine is one of the major components of the conditioning regimen for hematopoietic stem cell transplantation (HSCT), and frequently causes severe oral mucositis. We have recently demonstrated that cytarabine is excreted into the saliva in patients receiving high-dose cytarabine, and proposed that it might locally and directly contribute to the development of oral mucositis. Therefore, this study was performed to assess whether removing the excreted cytarabine in the saliva by intensive mouth rinse during high-dose cytarabine infusion could reduce the incidence of oral mucositis. Fifteen patients with hematologic malignancies undergoing allogeneic HSCT who received total body irradiation (12 Gy) and high-dose cytarabine at a dose of 3 g/m(2) every 12 h for 4 days as a conditioning were evaluated. Patients were instructed to rinse their mouths using ice-cold water every 10 min, starting simultaneously with the 2-h cytarabine infusion and continuing up to 1 h after completion of each infusion. Oral mucositis was graded on a daily basis according to the National Cancer Institute, Common Toxicity Criteria. Thirty-five patients who previously underwent the same conditioning without mouth rinse served as controls. The incidence of Grades 2-3 and Grade 3 oral mucositis was significantly reduced in patients who performed mouth rinse as compared with the controls (40 vs. 80%, P = 0.009; 0 vs. 25. 7%, P = 0.02). In conclusion, mouth rinse during and shortly after high-dose cytarabine infusion could be an effective and inexpensive measure in reducing the incidence of moderate to severe oral mucositis caused by high-dose cytarabine. This finding strongly suggests the role of cytarabine excretion in the saliva in the development of cytarabine-associated oral mucositis.

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Fractionated total‐body irradiation preceding high‐dose cytosine arabinoside as a preparative regimen for bone marrow transplantation in children with acute leukemia

Cited by 8 publications

References 15 publications

Reduced efficacy of topical corticosteroid in preventing cytarabine-induced kerato-conjunctivitis in patients receiving high-dose cytarabine and total body irradiation for allogeneic hematopoietic stem cell transplantation

Reduced efficacy of topical corticosteroid in preventing cytarabine-induced kerato-conjunctivitis in patients receiving high-dose cytarabine and total body irradiation for allogeneic hematopoietic stem cell transplantation

Addition of high-dose Ara-C to the BMT conditioning regimen reduces leukemia relapse without an increase in toxicity

Efficacy of mouth rinse in preventing oral mucositis in patients receiving high-dose cytarabine for allogeneic hematopoietic stem cell transplantation

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