Fludarabine and melphalan combined with in vivo alemtuzumab is a promising transplantation regimen for patients with AML or MDS and low tumor burden. For patients with active disease, this regimen provides at best modest palliation. Despite a low incidence of GVHD, transplantation is still associated with considerable nonrelapse mortality in patients with decreased performance status.

We describe treatment, outcomes and prognostic factors for patients who relapse following transplantation with a reduced intensity conditioning regimen. Seventy consecutive patients with high-risk myeloid malignancies underwent transplant and 25 (36%) relapsed, a median of 120 days later. The median percentage of bone marrow blasts at relapse was 24, the median donor chimerism was 73% and new karyotypic abnormalities occurred in 8 out of 20 (40%) evaluable patients. Twenty-one patients (84%) received aggressive treatment for relapse, including chemotherapy (60%), second hematopoietic cell transplantation (HCT; 52%) and/or donor lymphocyte infusion (DLI; 12%). Thirteen achieved a complete response (CR) and four remain in CR. Median overall survival (OS) after relapse was 6 months (95% confidence interval ¼ 2.7-9.9 months), and actuarial 1 year OS was 24%. Most deaths were due to disease progression (17/20, 85%). We did not observe an advantage for cellular therapy (DLI or second transplant) compared to chemotherapy. Salvage therapy for relapse after reduced intensity HCT is feasible, associated with low treatment-related mortality, and may result in prolonged survival in select patients. Studies exploring the optimal treatment for relapse following reduced intensity HCT are warranted.

Summary:characteristics. and high-grade lymphomas, high-dose chemotherapy (HDC) with autologous stem cell rescue (SCR) provides adults (ages 18-60 years; median 36) underwent alloBMT for lymphoma after failure of standard chemolong-term disease-free survival in 40-60% of patients who relapse with chemotherapy-sensitive disease, and has been therapy. Twenty-one had NHL and six had HD (nodular sclerosis). Thirteen patients had primary refractory disshown to be superior to conventional salvage chemotherapy alone. 2 Long-term survival for patients with primary refracease or chemotherapy-resistant relapses; two of these had relapsed after autoBMT. Three patients had tory or chemotherapy-resistant disease treated with HDC and autologous SCR, however, is only about 10%. 3 untested relapses (one of them had relapsed after autoBMT), and 11 had chemotherapy-sensitive relapses.Low-grade lymphomas are indolent disorders with a high rate of response to initial treatment and a median survival Twenty-four received HLA-matched bone marrow from a sibling (one twin); three received haploidentical marduration of 7-9 years. 3 Although aggressive chemotherapy regimens including HDC and autologous SCR in this group row cells. Nine (33%) died from lymphoma. Eleven (41%) died of treatment-related causes. Opportunistic of patients have shown progression-free survival rates of 50%, follow-up has been relatively short. 4,5 Again, patients infections were a substantial problem leading to eight of these deaths (30%). Six patients (22%) survive free with advanced, recurrent or refractory disease have had a very poor prognosis. of lymphoma 17-70 months post-BMT (median, 56 months); four had had sensitive relapses, one had had Several groups have begun examining the role of allogeneic bone marrow transplantation (alloBMT) for those a resistant relapse, and one had had nontested relapse. Three have chronic GVHD (limited in one; extensive in HD/NHL patients who are younger than 60 years of age and have a suitable HLA (human leukocyte antigen) comtwo). One HD patient who had relapsed after autoBMT remains in remission 19 months after alloBMT. No patible donor. Advantages of alloBMT include hematopoietic rescue with tumor-free marrow, the potential for a therapy-related myelodysplasia has been observed. We conclude that alloBMT has substantial morbidity in graft-versus-lymphoma effect leading to a lower incidence of relapse post-transplantation, and lower rates of therapyheavily pretreated lymphoma patients due to acute toxicity, infections and GVHD. However, 22% of our related leukemia. The few studies that have been performed using alloBMT have reported a 25-35% early mortality HD/NHL patients have had long-term disease-free survival.rate, with deaths secondary to graft-versus-host disease (GVHD), as well as regimen-related toxicities and infecKeywords: allogeneic marrow transplantation; Hodgkin's; lymphoma tion. 6 However, lower than expected relapse rates have been observed in surviving patients, thus suggesting the possibility of an immune-...

Summary:Since approximately 30% of leukemia patients relapse after allogeneic BMT using total body irradiation (TBI)-based preparative regimens, treatment intensity may be suboptimal. The killing of leukemia cells is proportional to the radiation absorbed dose. We studied the feasibility and toxicity of escalating the doses of fractionated TBI above our previous prescription of 13.5 Gy. Sixteen evaluable patients with advanced hematologic malignancies were treated with twice daily TBI using a highenergy source (18-24 MV). The first patient cohort (n = 11) received a total dose of 14.4 Gy in nine fractions, and the second cohort (n = 5) received doses escalated to 15.3 Gy. All patients received high-dose etoposide (60 mg/kg) and allogeneic stem cell transplantation following the TBI. All patients had HLA-identical sibling donors. The median times for neutrophil and platelet engraftment were 13.5 and 12 days, respectively, and did not differ between the two cohorts. All but one patient developed treatment-related grade 3 or 4 mucositis. There were three cases of grade 4 pulmonary toxicity and three cases of grade 4 hepatic toxicity among the 14.4 Gy cohort, and one case each of grade 4 pulmonary and hepatic toxicities among the 15.3 Gy cohort. In most cases comorbid conditions contributed to these toxicities. Two patients had significant GVHD of the GI tract. Six relapses occurred, five (45%) in the 14.4 Gy cohort and one (20%) in the 15.3 Gy cohort. The 100-day treatment-related mortality rates were 9% and 20% for the 14.4 Gy and 15.3 Gy cohorts, respectively, and the median survivals were 226 and 201 days, respectively. We conclude that TBI dose escalation above the previously used 13.5 Gy dose is feasible using a high-energy source and high-dose etoposide. Acute and chronic toxicities were primarily related to GVHD, infection and relapse rather than to TBI. Since 1971, bone marrow transplantation (BMT) has been increasingly used in the treatment of patients with various malignant hematologic diseases including chronic myelogenous leukemia (CML), acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), multiple myeloma, chronic lymphocytic leukemia (CLL), non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD). 1-3 Marrow ablative chemoradiotherapy and allogeneic BMT offer potential cure for patients who are not curable with conventional therapy. For many patients transplanted over this time, total body irradiation (TBI) in standard doses of 12-13.5 Gy has been used together with cyclophosphamide or etoposide (VP-16) as the preparative regimen due to its substantial anti-tumor and immunosuppressive activities. [4][5][6][7][8][9][10][11][12] Since 20-30% of patients treated with TBI-based preparative regimens die from leukemia relapse, we postulated that treatment intensity is suboptimal. The killing of leukemia cells is proportional to the radiation absorbed dose. Few patients die from direct complications of TBI. Most often, the doses of concomitant chemotherapy have been escalated or a second or third...

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