A Phase I Study of Hypofractionated Tailored Total Marrow or Total Lymphoid Irradiation with Helical Tomotherapy Plus Chemotherapy As a Conditioning Regimen for Autologous Stem Cell Transplantation

We performed a phase I study on the combination of hypofractionated intensity modulated radiotherapy plus busulfan or melphalan as conditioning regimen for autologous stem cell transplantation in patients with acute leukemia and relapsed lymphoma.

Thirteen patients with a median age of 54 (range 36–67) years entered this trial. Eight patients had acute leukemia (7 AML and 1 ALL) and 5 patients relapsed lymphomas (3 HD and 2 NHL). All patients were treated with helical tomotherapy to obtain a precise conformation of the dose distribution with the highest spare as achievable normal tissue. The conditioning regimen for acute leukemia consisted of tandem total marrow irradiation and total body irradiation (12Gy in 3 days - single fraction per day); in particular, it was performed with 8Gy in 2 fractions for total marrow irradiation and 4Gy for total body irradiation, respectively. After 2 days rest, busulfan was given at the dose of 3,2 mg/kg body weight/day for 2 days.The conditioning regimen for lymphomas consisted of 12Gy in 3 days (single fraction per day) delivered to the entire major lymph node-bearing areas, from the levels of the neck to the inguinal region, including the thymus and spleen; after 2 days rest, melphalan was given at the dose of 140 mg/m². The median number of CD34⁺ cells infused was 4,2 × 10⁶/kg BW (range 2,0–10,0).

The median doses delivered to organ at risk with total lymphoid irradiation was 40% to 80% respect to the target volume dose, while the median dose reduction achieved with total marrow irradiation ranged from 30% to 65% with the largest reduction (−50%–65%) obtained for brain, larynx, liver, lungs and kidneys. All patients showed complete engraftment after a median time of 14 days (range 11–21). The transfusion support for each patient was 1–2 units of packed red blood cells and 2–3 units of platelets concentrates. Seven out of 13 (53%) patients experienced fever of undetermined origin which lasted for a mean period of 3 days (range 1–6) and solved after broad spectrum i.v. antibiotics/antimicotics; furthermore, 6 patients developed grade 3/4 mucositis and total parenteral nutrition was administered for a mean time of 6 days (range 4–8). None of the patients experienced other grade 3/4 non hematologic toxicity.

Our preliminary results show that hypofractionated-intensity modulated radiotherapy with helical tomotherapy plus chemotherapy is a safe conditioning regimen for autologous stem cell transplantation in acute leukemia and lymphomas. Our report is the first that investigated the feasibility of an high dose hypofractionated radiotherapy regimen to achieve an higher cell kill rate. According to this preliminary experience, we are extending this approach to multiple myeloma and to low risk acute leukemia patients in first complete remission.

No relevant conflicts of interest to declare.