5. Toxicity possibly associated with retinoic acid after high‐dose chemotherapy followed by autologous haematopoietic stem cell transplantation.
| Study | Study design | Type of HSCT | Type of RA | Dose1 | Pat2 | Type of adverse event (N of affected participants) |
| Clarke 2003 | CR | PBSCT | CRA | 160 | 1 | Pneumocystis carinii pneumonia (1) |
| Cross 2009 | CR | NR | CRA | 160 | 1 | Hypercalcaemia (1), osteoblastic lesions (1) |
| De Kraker 2008 | SA‐IS | BMT or PBSCT | CRA | 160 | 44 | NR |
| Granger 2012 | SA‐IS | PBSCT | CRA | 160 | 33 | NR |
| Hamidieh 2012 | SA‐IS | PBSCT | CRA | 120 to 160 | 14 | NR |
| Haysom 2005 | CR | BMT | CRA | 160 | 2 | Bone marrow transplant nephropathy (2) |
| Inamo 1999 | CR | BMT | CRA | 33 to 1023 | 1 | Growth failure (1) |
| Khan 1996 | SA‐IS | BMT | CRA | 100 to 200 | 31 | Grade 3/4 toxicity of skin, liver and hypercalcaemia correlated with peak serum levels of CRA |
| Kletzel 2002 | SA‐IS | PBSCT | CRA | 160 | 12 | Ataxia (1) |
| Kogner 2004 | RCT | BMT | CRA | NR | 12 | NR |
| Kohler 2000 | RCT | NR | CRA | 15 to 224 | NR | Dry skin (47), cheilitis (24), bone pain (16), other (13) |
| Kreissman 2013 | RCT | PBSCT | CRA | 160 | 192 | Grade 3 toxic effects: hypertension (4), hematuria (2), elevated serum creatinine (2), proteinuria (3); purged and non‐purged transplantation group combined |
| Kushner 2003a | CS | NR | CRA | 160 | 1 | Cheilitis (1) |
| Laskin 2011 | CS | NR | CRA | NR | 20 | NR |
| Marabelle 2009 | CR | NR | CRA | 160 | 3 | Hypercalcaemia (3) |
| Marmor 2008 | CR | NR | Fenretinide | 666 to 20515 | 2 | Rod electroretinogram suppression (2) |
| Mastrangelo 2011 | SA‐IS | PBSCT | CRA | 160 | 8 | NR |
| Matthay 2006 | SA‐IS | BMT | CRA | 160 | 22 | NR |
| Mugishima 2008 | CR | BMT | CRA | 130 to 400 | 2 | Hypercalcaemia (2) |
| Nishimura 1997 | CR | BMT | CRA | 33 to 1023 | 1 | Generalised metaphyseal modification (1) |
| Park 2011 | SA‐IS | PBSCT | CRA | 160 | 30 | NR |
| Rayburg 2009 | CR | NR | Fenretinide | 2210 | 1 | Langerhans cell histiocytosis (1) |
| Saarinen‐Pihkala 2012 | SA‐IS | BMT or PBSCT | CRA | NR | 36 | NR |
| Simon 2011 | SA‐IS | NR | CRA | 160 | 75 | NR |
| Sirachainan 2008 | CR | NR | CRA | 140 | 1 | NR |
| Sung 2007 | SA‐IS | PBSCT | CRA | 125 | 44 | Skin eruption, particularly face |
| Turman 1999 | CR | BMT | CRA | 160 | 2 | Bone marrow transplant nephropathy (2) |
| Veal 2007 | SA‐IS | NR | CRA | 160 | 28 | Mild skin toxicity (9), cheilitis (1), hypercalcaemia (2) |
| Veal 2013 | SA‐IS | NR | CRA | 160 | 103 | Grade 3 ‐ 4 skin toxicity or cheilitis (5) |
| Villablanca 1993 | SA‐IS | BMT | CRA | 100 to 200 | 49 | Dose‐limiting toxicity of hypercalcaemia (3), arthralgia and myalgia (1), grade 1 to 3 hypercalcaemia (9) |
| Villablanca 1995 | SA‐IS | BMT | CRA | 200 | 51 | Hypercalcaemia (3), rash (2) |
| Villablanca 2011 | SA‐IS | NR | Fenretinide | 1800 to 2475 | 626 | Rash (1), diarrhoea (1), nausea (2), vomiting (1), nyktalopia (1), abdominal pain (4) |
| Yu 2010 | RCT | NR | CRA | 160 | 108 | "Few toxic effects" |
Notice: Studies presented in this table were not eligible for inclusion in this review.
1Dose in mg/m2/day. The unit mg/kg may be transformed to mg/m2. The average body weight, body length, and body surface of a 6‐month‐old child may be 8 kg, 67 cm, and 0.39 m2, thus 8 kg divided by 0.39 m2 is roughly equalto a conversion factor of 20 (CDC 2000a). This factor increases continuously with age. The average body weight, body length, body surface of an 11‐year‐old child may be 36 kg, 143 cm, and 1.20 m2, thus 36 kg divided by 1.20 m2 is roughly equal to a conversion factor of 30 (CDC 2000b). The unit mg per day may be transformed to m2 per day. For example, 300 mg per day may vary on average between 769 mg/m2 (300 mg/0.39 m2) and 250 m2 (300 mg/1.20 m2)
2Participants treated with retinoic acid after HDCT followed by autologous HSCT acid and evaluated for toxicity.
3Inamo 1999; Nishimura 1997: Patients received retinoic acid at a dose of 40 mg per day. The daily dose may vary on average between 102 mg/m2 (40 mg/0.39 m2) and 33 m2 (40 mg/1.20 m2)
4Kohler 2000: Participants received retinoic acid at a dose of 0.75 mg/kg per day. The daily dose may vary on average between 15 mg/m2 (0.75 mg/kg * 20) and 22 mg/m2 (0.75 mg/kg * 30).
5Marmor 2008: Participants received retinoic acid at a dose of 800 mg per day. The daily dose may vary on average between 2051 mg/m2 (800 mg/0.39 m2) and 666 m2 (800 mg/1.20 m2).
6Villablanca 2011: 51 of the 62 participants received HSCT.
BMT: bone marrow transplantation; CR: case report; CS: case series; CRA: 13‐cis‐retinoic acid; HDCT: high‐dose chemotherapy; HSCT: haematopoietic stem cell transplantation; N: number of participants; NR: not reported; PBSCT: peripheral blood stem cell transplantation; RA: retinoic acid; SA‐IS: single‐arm intervention study such as phase‐1 or phase‐2 clinical trial