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| Case | Age/sex | ATRA dosage (mg/m2/day) | ATRA treatment duration prior to PC occurrence [treatment cycle] | PC presentation | PC treatment | PC resolution (days) | Long-term follow up/comments |
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| Index case | 38/female | 45 mg/m2/day | 17 days [induction] | Headache, papilledema, 300 mm H2O CSF pressure, nausea, vomiting, and photosensitivity | Acetazolamide, antiemetics, and analgesics; withdrawal of ATRA and fluconazole | 5 days after withdrawal of ATRA and 1 day after withdrawal of fluconazole | Successful ATRA rechallenge; CR at 12+ months |
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| Jeddi et al. [13] | 35/female | 45 mg/m2/day | 25 days [induction] | Headache, papilledema, 500 mm H2O CSF pressure, diplopia, and strabismus | Corticosteroids, repeated lumbar punctures; withdrawal of ATRA | 2 days after withdrawal of ATRA | Participant in Spanish PETHEM LPA99 trial |
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| Vanier et al. [14] | 4/male | 1st course: 45 mg/m2/day
2nd course: 33.75 mg/m2/day 3rd course: Initially 13.5 mg/m2/day, increased to 45 mg/m2/day | 21 days−1 day after beginning 100 mg/day fluconazole [induction] | Headache, papilledema, >200 mm H2O CSF pressure, and vomiting | 1st course: Withdrawal of ATRA
2nd course: ATRA dose reduction followed by withdrawal
3rd course: Further ATRA dose reduction and withdrawal of fluconazole | 1st course: 1 day after withdrawal of ATRA
2nd course: N/A
3rd course: 1 day after withdrawal of fluconazole (ATRA maintained) | Multiple ATRA rechallenges: unsuccessful 1st rechallenge at 75% of therapeutic dose, successful 2nd rechallenge at 30% of therapeutic dose, tolerated increase to therapeutic dose after fluconazole withdrawal |
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| Visani et al. [19] | 16/male | 45 mg/m2/day | 31 days [induction] | Headache, papilledema, diplopia, tinnitus, and visual field changes | Acetazolamide; withdrawal of ATRA, therapeutic lumbar puncture | 15 days after withdrawal of ATRA | Acetazolamide use ineffective but subsequent lumbar puncture successfully relieved PC signs/symptoms; CR at 17+ months |
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| Yeh et al. [20] | 27/female | 45 mg/m2/day | 23 weeks [maintenance] | Headache, papilledema, 230 mm H2O CSF pressure, and blurred vision | Withdrawal of ATRA | 4 weeks after withdrawal of ATRA | N/A |
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| Schroeter et al. [38] | 8/female | 25 mg/m2/day | 65 days [consolidation] | Headache, papilledema, diplopia, nausea, vomiting, and left cranial nerve IV palsy | Corticosteroids, mannitol, acetazolamide, and analgesics; withdrawal of ATRA | 1 week after withdrawal of ATRA | CR at day 90+ |
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Guirgis MF and Lueder GT [40] | Case A: 16/female | 1st course: 70 mg/day
2nd course: N/A | 1st course: 1 week [induction]
2nd course: 4 weeks [induction] | 1st course: headache, papilledema, and visual field changes
2nd course: headache, papilledema, 370 mm H2O CSF pressure | 1st course: lumbar puncture
2nd course: acetazolamide (250 mg BID) and therapeutic lumbar puncture | 1st course: immediate symptomatic relief after lumbar puncture
2nd course: 5 months after administration of acetazolamide and 6 months 9 days after 1st withdrawal of ATRA | Multiple ATRA rechallenges with symptom recurrence during 2nd ATRA course, PC resolution at 5+ months |
| Case B: 17/male | 90 mg/day | 2 weeks [induction] | Headache, papilledema, and visual field changes | Acetazolamide (250 mg TID) | 4 weeks after administration of acetazolamide | Maintained ATRA despite signs/symptoms of PC, acetazolamide slowly tapered over two months following PC resolution, persistent blind spots but no papilledema or other symptoms during follow-up |
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| Chen et al. [41] | 17/female | 45 mg/m2/day | 8 weeks [maintenance] | Headache, papilledema, 265 mm H2O CSF pressure, diplopia, esotropia, and left cranial nerve VI palsy | Withdrawal of ATRA | 4 weeks after withdrawal of ATRA | N/A |
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| Selleri et al. [42] | 31/female | 45 mg/m2/day | 10 months of continuous ATRA following APL relapses × 2 [maintenance] | Headache, papilledema, 580 mm H2O CSF pressure, diplopia, and blurred vision | Withdrawal of ATRA | 3 weeks after withdrawal of ATRA | Patient underwent ASCT and in CR at 24 months |
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| Naderi et al. [43] | 20/female | 40 mg/m2/day | 13 days [induction] | Headache, papilledema, 390 mm H2O CSF pressure, nausea, and vomiting | Therapeutic lumbar punctures | Day 27 of continued ATRA treatment | Maintained ATRA despite signs/symptoms of PC |
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| Tiamkao et al. [44] | 35/female | 60 mg/day | 14 days [induction] | Headache, papilledema, 300 mm H2O CSF pressure, blurred vision, and visual field changes | Withdrawal of ATRA | 1 week after withdrawal of ATRA | N/A |
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| Mishra et al. [45] | 6/female | 45 mg/m2/day | 16 days [induction] | N/A | Withdrawal of ATRA | N/A | Developed Sweet’s Syndrome and benign thymic hyperplasia after induction therapy, achieved a CR (timeline N/A) |
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| Sakamoto et al. [46] | 11/male | 1st course: initially 47 mg/m2/day, decreased to 39 mg/m2/day
2nd course: 39 mg/m2/day | 1st course: 10 days [induction]
2nd course: 2 days [maintenance] | Headache, nausea | 1st course: glycerol; ATRA dose reduction followed by ATRA withdrawal
2nd course: biphosphonate for hypercalcemia | 1st course: 1 week after withdrawal of ATRA
2nd course: N/A | Glycerol and ATRA dose reduction ineffective but subsequent ATRA withdrawal relieved PC signs/symptoms; hypercalcemia at day 25, biphosphonate use successfully resolved hypercalcemia and PC; CR at day 46+ |
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| Decaudin et al. [47] | 16/male | 45 mg/m2/day | 13 days [induction] | Headache, papilledema, 260 mm H2O CSF pressure, diplopia, photosensitivity, nuchal stiffness, and bilateral cranial nerve VI paresis | Therapeutic lumbar punctures | 3 weeks after withdrawal of ATRA | Maintained ATRA despite signs/symptoms of PC; CR at 12+ months |
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| Sano et al. [48] | 18/male | 45 mg/m2/day | 23 days [induction] | Headache, papilledema, 350 mm H2O CSF pressure, diplopia, and nausea | Glycerin, withdrawal of ATRA | 6 days after withdrawal of ATRA | CR at day 29 |
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| Machner et al. [49] | 20/female | 1st course: 45 mg/m2/day
2nd course: 45 mg/m2/day | 14 days [induction] | 1st course: headache, papilledema, 500 mm H2O CSF pressure, blurred vision, visual field changes
2nd course: headache | 1st course: lumbar puncture, acetazolamide (1000 mg/day) and analgesics, withdrawal of ATRA
2nd course: continued acetazolamide | 1 day after withdrawal of ATRA following
2nd course | Successful ATRA rechallenge caused minimal toxicity (low level stable headache), CR at day 30+, NED and without PC at 3 months |
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| Gallipoli [50] | 31/female | 45 mg/m2/day | 17 days [induction] | 1st CT course: headache, papilledema, 600 mm H2O CSF pressure, diplopia, and right cranial nerve VI palsy
2nd–4th CT courses and maintenance therapy: headache and elevated CSF pressure | 1st CT course: therapeutic lumbar punctures, dexamethasone, and acetazolamide, withdrawal of ATRA
2nd–4th CT courses and maintenance therapy: therapeutic lumbar punctures and acetazolamide (1000 mg/day) | 1st CT course: N/A
2nd–4th CT courses and maintenance therapy: N/A | Multiple ATRA rechallenges at full dose induced PC during consolidation and maintenance therapy, PC signs/symptoms steadily resolved during all CT courses and maintenance therapy (timeline N/A), CR after induction therapy (timeline N/A) |
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| Varadi et al. [51] | 17/female | 45 mg/m2/day | N/A [maintenance] | Headache, papilledema, 340 mm H2O CSF pressure, diplopia, blurred vision, and right cranial nerve VI palsy | Dexamethasone and acetazolamide, withdrawal of ATRA, allogeneic BMT | N/A | 1st ATRA course induced hyperleukocytosis, ATRA rechallenge induced APL relapse and PC symptoms; allogeneic BMT from HLA-identical brother, achieved a CR (timeline N/A), NED 27 months post-BMT |
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| Naithani et al. [52] | 9/male | 1st course: 45 mg/m2/day
2nd course: 10 mg bid on day 16, escalated to 30 mg bid on day 19 and 45 mg/m2/day on day 21
3rd course: “low dose” on day 26, escalated to 30 mg bid | 1st course: 12 days [induction]
2nd course: 7 days [induction]
3rd course: N/A (no PC) | 1st course: headache, papilledema, diplopia, and vomiting
2nd course: headache, vomiting
3rd course: N/A (no PC) | 1st course: Acetazolamide and mannitol, withdrawal of ATRA
2nd course: Withdrawal of ATRA
3rd course: N/A (no PC) | 1/2 day after withdrawal of ATRA following
2nd course | Multiple ATRA rechallenges with successful 2nd rechallenge, CR at 5 weeks |
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| Colucciello [53] | 30/male | N/A | 14 days [induction] | Headache, papilledema, 225 mm H2O CSF pressure, diplopia, and cranial nerve VI palsy | Withdrawal of ATRA | 6 weeks after withdrawal of ATRA | Achieved a CR with multiagent CT (timeline N/A) |
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| Ganguly [54] | 43/male | 45 mg/m2/day | 1st course: 9 days [induction]
2nd course: 7 days [maintenance] | Headache, papilledema | 1st course: acetazolamide (500 mg/day)
2nd course: Withdrawal of ATRA | N/A | Multiple ATRA rechallenges during maintenance therapy, 2nd rechallenge successful with prophylactic acetazolamide (500 mg/day) |
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| Smith et al. [62] | 6/male | Initially 45 mg/m2/day, escalated to 80 mg/m2/day | 7–10 days [induction] | Headache, papilledema, and elevated opening CSF pressure | Withdrawal of ATRA | N/A | Opening CSF pressure elevated but not measured, successful ATRA rechallenge (60 mg/m2/day) led to 5 month ATRA course following neurologic symptom resolution |
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