Transplant conditioning regimens

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Autologous (auto) stem cell transplant

BEAC

BEAC: BiCNU, Etoposide, Ara-C, Cyclophosphamide

Regimen

Autologous blood stem cells are infused on day 0.

• Carmustine (BiCNU) 300 mg/m2 IV on day -7
• Etoposide (Vepesid) 800 mg/m2 IV on days -6 to -3
• Cytarabine (Cytosar) 800 mg/m2 IV on days -6 to -3
• Cyclophosphamide (Cytoxan) 35 mg/kg IV on days -6 to -3

Supportive medications:

• Filgrastim (Neupogen) 5 mcg/kg SC daily starting on day +1, continued until there are 3 consecutive days with ANC ≥1000
• Prophylaxis against opportunistic infections and management of febrile neutropenia per "active protocols"

References

1. Jo JC, Kang BW, Jang G, Sym SJ, Lee SS, Koo JE, Kim JW, Kim S, Huh J, Suh C. BEAC or BEAM high-dose chemotherapy followed by autologous stem cell transplantation in non-Hodgkin's lymphoma patients: comparative analysis of efficacy and toxicity. Ann Hematol. 2008 Jan;87(1):43-8. Epub 2007 Aug 21. link to original article contains protocol PubMed

BEAM

BEAM: BiCNU, Etoposide, Ara-C, Melphalan

Regimen (Jo, et al. 2008)

Autologous blood stem cells are infused on day 0.

• Carmustine (BiCNU) 300 mg/m2 IV on day -6
• Etoposide (Vepesid) 200 mg/m2 IV on days -5 to -2
• Cytarabine (Cytosar) 400 mg/m2 IV on days -5 to -2
• Melphalan (Alkeran) 140 mg/m2 IV on day -1

Supportive medications:

• Filgrastim (Neupogen) 5 mcg/kg SC daily starting on day +1, continued until there are 3 consecutive days with ANC ≥1000
• Prophylaxis against opportunistic infections and management of febrile neutropenia per "active protocols"

Alternate regimen #1 (Stewart, et al. 2006)

Autologous blood stem cells are infused on day 0.

• Carmustine (BiCNU) 300 mg/m2 IV on day -6
• Etoposide (Vepesid) 100 mg/m2 IV Q12H on days -5 to -2 (8 total doses)
• Cytarabine (Cytosar) 200 mg/m2 IV Q12H on days -5 to -2 (8 total doses)
• Melphalan (Alkeran) 140 mg/m2 IV on day -1

Supportive medications:

• Patients <70 kg: Filgrastim (Neupogen) 300 mcg SC daily starting on day +7 after stem cell transplant
• Patients >70 kg (reference did not clarify which dosage to use for patients who are exactly 70 kg): Filgrastim (Neupogen) 480 mcg SC daily starting on day +7 after stem cell transplant
• Trimethoprim/Sulfamethoxazole (Bactrim DS) (160/800 mg) PO BID on Monday and Thursdays, until 6 months after BEAM

While ANC <500

• Ciprofloxacin (Cipro) 500 mg PO BID
• Fluconazole (Diflucan) 100 mg PO daily or mycostatin 500,000 units swish & swallow QID
• Acyclovir (Zovirax) 400 mg PO TID

Alternate regimen #2 (Josting, et al. 2005)

Paper did not specify which day peripheral blood stem cells were administered.

• Carmustine (BiCNU) 300 mg/m2 IV on day 1
• Etoposide (Vepesid) 150 mg/m2 IV Q12H on days 2-5 (8 total doses)
• Cytarabine (Cytosar) 200 mg/m2 IV Q12H on days 2-5 (8 total doses)
• Melphalan (Alkeran) 140 mg/m2 IV on day 1

References

1. Josting A, Sieniawski M, Glossmann JP, Staak O, Nogova L, Peters N, Mapara M, Dörken B, Ko Y, Metzner B, Kisro J, Diehl V, Engert A. High-dose sequential chemotherapy followed by autologous stem cell transplantation in relapsed and refractory aggressive non-Hodgkin's lymphoma: results of a multicenter phase II study. Ann Oncol. 2005 Aug;16(8):1359-65. Epub 2005 Jun 6. link to original article contains protocol PubMed
2. Stewart DA, Bahlis N, Valentine K, Balogh A, Savoie L, Morris DG, Jones A, Brown C, Russell JA. Upfront double high-dose chemotherapy with DICEP followed by BEAM and autologous stem cell transplantation for poor-prognosis aggressive non-Hodgkin lymphoma. Blood. 2006 Jun 15;107(12):4623-7. Epub 2006 Feb 7. link to original article contains protocol PubMed
3. Jo JC, Kang BW, Jang G, Sym SJ, Lee SS, Koo JE, Kim JW, Kim S, Huh J, Suh C. BEAC or BEAM high-dose chemotherapy followed by autologous stem cell transplantation in non-Hodgkin's lymphoma patients: comparative analysis of efficacy and toxicity. Ann Hematol. 2008 Jan;87(1):43-8. Epub 2007 Aug 21. link to original article contains protocol PubMed

TAM6

Regimen

• TBI 10 Gy over 3 days using twice-daily fractions
• Cytarabine (Cytosar) 1500 mg/m2 IV Q12H (4 total doses)
• Melphalan (Alkeran) 140 mg/m2 IV

Peripheral stem cells are infused on day 0

Supportive medications: "Antimicrobial prophylaxis and use of G-CSF or erythropoietin were permitted according to physician decision."

References

1. Delarue R, Haioun C, Ribrag V, Brice P, Delmer A, Tilly H, Salles G, Van Hoof A, Casasnovas O, Brousse N, Lefrere F, Hermine O; for the Groupe d'Etude des Lymphomes de l'Adulte (GELA). CHOP and DHAP plus rituximab followed by autologous stem cell transplantation in mantle cell lymphoma: a phase 2 study from the Groupe d'Etude des Lymphomes de l'Adulte. Blood. 2013 Jan 3;121(1):48-53. Epub 2012 Jun 20. link to original article contains protocol PubMed

Allogeneic (allo) stem cell transplant

BEAM

BEAM: BiCNU, Etoposide, Ara-C, Melphalan

Regimen

Day 0 is the day of transplantation.

• Carmustine (BiCNU) 300 mg/m2 IV on day -6
• Etoposide (Vepesid) 200 mg/m2 IV BID on days -5 to -2
• Cytarabine (Cytosar) 200 mg/m2 IV BID on days -5 to -2
• Melphalan (Alkeran) 140 mg/m2 IV on day -1

Supportive medications:

• Filgrastim (Neupogen) 5 mcg/kg SC daily, starting day 7 and continued until engraftment
• GVHD prophylaxis with tacrolimus and methotrexate
• "Prophylactic antibiotics"

References

1. Przepiorka D, van Besien K, Khouri I, Hagemeister F, Samuels B, Folloder J, Ueno NT, Molldrem J, Mehra R, Körbling M, Giralt S, Gajewski J, Donato M, Cleary K, Claxton D, Braunschweig I, Andersson B, Anderlini P, Champlin R. Carmustine, etoposide, cytarabine and melphalan as a preparative regimen for allogeneic transplantation for high-risk malignant lymphoma. Ann Oncol. 1999 May;10(5):527-32. link to original article contains protocol PubMed

Fludarabine Busulfan - once daily Flu/Bu

Regimen

Day 0 is the day of transplantation.

• Fludarabine (Fludara) 50 mg/m2 IV daily on days -6 to -2
• Busulfan (Myleran) 3.2 mg/kg (ideal body weight) IV daily over 3 hours on days -5 to -2

Supportive medications:

• Phenytoin (Dilantin) "loading" PO/IV, dosed to maintain therapeutic levels of 40-80 umol/L on days -5 to -2
• Ciprofloxacin (Cipro) 500 mg PO BID as prophylaxis
• Trimethoprim/Sulfamethoxazole (Bactrim DS) (dose not specified in reference, but assume 160/800 mg dose) PO 2 times a week as PCP prophylaxis
• No routine fungal prophylaxis
• No routine use of growth factors
• CMV negative blood

Acute GVHD prophylaxis:

• Antithymocyte globulin (Thymoglobulin, rabbit ATG) 0.5 mg/kg IV on day -2; 2 mg/kg/day IV on days -1 and 0 (total dose of 4.5 mg/kg)
• Cyclosporine modified (Neoral) or Cyclosporine non-modified (Sandimmune) PO/IV BID, with doses adjusted to maintain cyclosporine levels of 150-400 umol/L
• Methotrexate (MTX) 15 mg/m2 on day 1; 10 mg/m2 on days 3, 6, 11
• Folinic acid (Leucovorin) 5 mg started 24 hours after each dose of methotrexate and continued Q6H until 12 hours before the next dose of methotrexate

References

1. Russell JA, Tran HT, Quinlan D, Chaudhry A, Duggan P, Brown C, Stewart D, Ruether JD, Morris D, Glick S, Gyonyor E, Andersson BS. Once-daily intravenous busulfan given with fludarabine as conditioning for allogeneic stem cell transplantation: study of pharmacokinetics and early clinical outcomes. Biol Blood Marrow Transplant. 2002;8(9):468-76. link to original article contains verified protocol PubMed

Low-dose TBI and Fludarabine

Regimen

Day 0 is the day of transplantation.

• Fludarabine (Fludara) 30 mg/m2 IV daily on days -4 to -2

TBI 2 Gy at a rate of 0.07-0.20 Gy/min on day 0

Acute GVHD prophylaxis: Cyclosporine or tacrolimus + MMF, details not specified

References

1. Gyurkocza B, Storb R, Storer BE, Chauncey TR, Lange T, Shizuru JA, Langston AA, Pulsipher MA, Bredeson CN, Maziarz RT, Bruno B, Petersen FB, Maris MB, Agura E, Yeager A, Bethge W, Sahebi F, Appelbaum FR, Maloney DG, Sandmaier BM. Nonmyeloablative allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia. J Clin Oncol. 2010 Jun 10;28(17):2859-67. doi:10.1200/JCO.2009.27.1460. Epub 2010 May 3. link to original article contains protocol PubMed