Regimen
Disease states treated
Comments
Cy + ATG + / – TBI
Aplastic anemia
TBI added for unrelated donors (URD)
tBu–Cy
AML, ALL, CLL, CML, NHL, MM, MDS
The busulfan exposure target varies by disease which is attained by pharmacokinetic monitoring
Cy–TBI
AML, ALL, CLL, NHL, MDS
–
BEAM
NHL, HD, MM
–
Table 6.2
Common RIC regimens
Regimen | Disease states treated | Comments |
|---|---|---|
Bu–Flu | AML, ALL, CLL | – |
Bu–Flu–TBI | AML, ALL, CLL | – |
Flu–Mel | NHL, MM | – |
Flu–TBI | AML, ALL, CLL | – |
TBI–200 cGY | AML, ALL, CLL | More rapidly paced disease may require more aggressive therapy. This is considered a nonmyeloablative regimen which is the least intense of the RIC regimens |
Flu–Cy–R | NHL, CLL | – |
Increasingly, in both adult and children who do not have a related stem cell donor, cord blood progenitor cells are being used as a stem cell source for their allogeneic HSCT. These require different conditioning regimens (Table 6.3) as well as changes in associated supportive care and immune suppression.
Table 6.3
Common conditioning regimens for cord blood transplants
Regimens | Disease states treated | Comments |
|---|---|---|
Flu–TBI (ablative) | AML, ALL, CML, MDS, NHL | Engraftment occurs approximately 2–3 weeks later than with other stem cell sources. Dual cord blood units often used for adults |
Cy–Flu–TT–TBI | AML, ALL MDS | Dual cord blood units often used for adults |
Cy–Flu–TBI | AML | – |
TT–Bu–Flu–rATG | AML, ALL, NHL, CML, MDS | Single cord blood unit used for adults and children |
In the autologous setting, high-dose therapy with stem cell support is frequently used to salvage relapsed or persistent disease, as well as to consolidate or prolong cancer remission. Sequential or tandem stem cell transplants are used in some disease states to further deepen a remission, increase the chance for cure, or facilitate delivery of a high dose regimen (Table 6.4).
Table 6.4
Common autologous conditioning regimens
Regimen | Disease states treated | Comments |
|---|---|---|
Bu16–Etoposide | AML | Note: despite ablative dose of Bu this is used in the autologous setting |
BEAM | NHL, HD | – |
BuMelTT | NHL, HD | – |
Carbo–Etoposide | Germ cell | May be done in tandem |
Carbo–Etoposide–Cy | Germ cell | May be done in tandem |
Cy–Etoposide–TBI | NHL, HD | – |
CBV | NHL, HD | – |
Melphalan | MM, Amyloid | May be done in tandem |
6.1 Conditioning Agents
Most conditioning agents are associated with pancytopenia , sterility, and alopecia in the doses used in myeloablative regimens. Mucositis may encompass the entire gastrointestinal (GI) tract and result in stomatitis, esophagitis, nausea, vomiting (see Table 6.5 for prophylaxis) , and diarrhea (see Chap. 21). Selected toxicities and important aspects of care are presented, as these are unique or more prevalent in the high-dose therapy setting. On a day-to-day basis, these effects may require additional therapy or attention to specific patient-care techniques to manage the patient and minimize morbidity (see Table 6.6 for dosing guidance to individualize dose for specific patients attributes):
Table 6.5
Antiemetic dosing
Agent | Risk | Antiemetic regimen | Comments |
|---|---|---|---|
Antithymocyte globulin | Low | None needed | Other premedications required |
Busulfan | Moderate to high | Ondansetron 8 mg PO Q 6 h or 24 mg PO daily | Dexamethasone 20 mg daily with once daily ondansetron no dexamethasone required for every 6 hour busulfan dosing |
Carboplatin | High | Ondansetron 24 mg PO or 8 mg IV prior to first daily chemotherapy dose | Dexamethasone 20 mg daily with each daily ondansetron |
Carmustine | High | Ondansetron 24 mg PO or 8 mg IV prior to first daily chemotherapy dose | Dexamethasone 20 mg daily with each daily ondansetron |
Clofarabine | Low | Ondansetron 8 mg PO daily. 16 mg (8 mg IV) if other chemotherapy agents given | Dexamethasone 8–12 mg daily with each daily ondansetron |
Cyclophosphamide | High | Ondansetron 24 mg PO or 8 mg IV prior to first daily chemotherapy dose.Consider adding aprepitant each day cyclophosphamide is given plus 1 additional day or fosaprepitant once on first day of cyclophosphamide | Dexamethasone 20 mg daily with each daily ondansetron. Dose adjust dexamethasone if aprepitant used |
Cytarabine | Low (< 1000 mg/m2/day) | Ondansetron 8 mg PO daily. 16 mg PO (8 mg IV) if other chemotherapy agents given | Dexamethasone 8 mg daily with each daily ondansetron |
Etoposide | Moderate to high | Ondansetron 24 mg PO or 8 mg IV prior to first daily chemotherapy dose | Dexamethasone 20 mg daily with each daily ondansetron |
Fludarabine | Low | Ondansetron 8 mg PO daily.16 mg PO (8 mg IV) if other chemotherapy agents given. If only agent used that day may substitute 10 mg prochlorperazine for the ondansetron | Dexamethasone 8 mg daily with each daily ondansetron |
Melphalan | High | Ondansetron 24 mg PO or 8 mg IV prior to first daily chemotherapy dose. Consider adding aprepitant each day melphalan is given and for one additional day or fosaprepitant once on first day of cyclophosphamide | Dexamethasone 20 mg daily with each daily ondansetron. Dose adjust dexamethasone if aprepitant used |
Total body irradiation | High | Ondansetron 8 mg PO prior to each radiation fraction | Dexamethasone 20 mg daily with the first daily ondansetron |
Thiotepa | High | Ondansetron 24 mg PO or 8 mg IV prior to first daily chemotherapy dose | Dexamethasone 20 mg daily with each daily ondansetron |
Table 6.6
Chemotherapy dosing in conditioning regimens
Agent | Dosing | Dose adjustment for renal insufficiency | Additional information |
|---|---|---|---|
Alemtuzumab | Flat dosing in adults based upon regimen selected | No dose adjustment required for renal dysfunction | No dose adjustments for small or obese individuals |
Busulfan | Dose on ABW25 in adults (obese and nonobese) receiving per kilogram dosing or BSA based on TBW for square meter dosing. All regimens > 12 mg/kg PO equivalent are recommended to have PK targeting as appropriate for the disease state.Regimens using doses ≤ 12 mg/kg PO equivalent do not have sufficient information to recommend routine PK monitoring at this time Pediatrics should be dosed upon TBW with similar monitoring guidelines | No dose adjustment required for renal dysfunction | -PK monitoring has reduced rate of SOS from ~ 20 % to < 5 % -AUC/Css targeting varies by regimen -For BuCy regimens, the MTD is 16 mg/kg PO equivalent over 4 days for adults |
Carboplatin | Dose adults on BSA based on TBW | If CrCl < 50, dose based on an AUC of seven per day using 24-h urine collection to estimate GFR or calculated CrCl | No dose adjustment required for BSA-dosed obese individuals. If using Calvert formula, dose based on 24-h urine collection derived from CrCl |
Carmustine | Dose adults on BSA based on TBW unless > 120 % IBW, then dose on BSA based on ABW25 | No dose adjustment required for renal dysfunction | Pulmonary toxicity > 50 % at 600 mg/m2 with multiple agent regimens. MTD of 1200 mg/m2 as single agent with 9.5 % pulmonary toxicity |
Clofarabine | Dose on BSA based on TBW | reduce 50% for CrCl 30–60 mL/min. Do not use for < 30 mL/min | No dose adjustments for obese individuals |
Cyclophosphamide | Dose on IBW for Cy 120 or 200 Exception: aplastic anemia for Cy 120 dose on TBW unless > 120 % IBW then ABW25 | For CrCl < 30, dose at 75 % of protocol dose | For obese patients, see dosing column |
Cytarabine | Dose on BSA based on TBW | No dose adjustment required if < 500 mg/m2 | No dose adjustment for obese patients |
Etoposide | Dose on ABW25 for milligrams per kilogram dosing and BSA based on TBW for BSA based dosing | Dose at 50 % for CrCl < 30; do not exceed 30 mg/kg | DLT of mucositis |
Fludarabine | Dose on BSA based on TBW | CrCl 17–40 ml/min dose at 80 % CrCl < 17 ml/min dose at 60 % | Post-treatment leukoencephalopathy still being studied for conditioning regimen doses more than 125 mg/m2 No dose adjustment for obesity |
Melphalan | Dose on BSA based on TBW | For CrCl < 40, dose at 70 mg/m2/day × 2 or 140 mg/m2 on 1 day for goal dose 200 mg/m2 | DLT of mucositis No dose adjustment for obesity as long as dose is < 3.6 mg/kg of ABW |
Pentostatin | Dose on BSA based on TBW | CrCl < 60, 75 % dose CrCl < 30, 40 % dose | No dose adjustment for obesity |
Thiotepa | Dose adults on BSA based on TBW unless > 120 % IBW then dose on BSA based on ABW40
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