Non-Ablative or Reduced Intensity Conditioning Regimens with Volunteer Unrelated Donor Progenitor Cell Transplantation.
Authors: Giralt Sergio , Logan Brent , Zhang Mei-Jei , McGaha Olivia , Ballen Karen , Emmanouilides Christos , Nath Rajneesh , Parker Pablo Miguel , Porter David , Sandmaier Brenda , Waller Edmund , Barker Juliet , Pavletic Steven , Weisdorf Daniel 
Published: April 2020

Purpose: Determine the current pattern of use of non-ablative and reduced intensity conditioning regimens (NST) with volunteer unrelated donor progenitor cell transplantation (URD-T) in patients with malignant diseases, and identify potential prognostic factors for transplant outcomes.

Patients and Methods: The National Marrow Donor Program (NMDP) database was queried to identify adult patients (greater than 18 years old) who had undergone an URD-T from 01/01/94 until 05/31/01, had a malignant disorder and received a conditioning regimen which fulfilled one of the following criteria: 500 cGy or less of total body irradiation, 9 mg/kg or less of total busulfan dose; 140 mg/m2 or less total melphalan dose and included a purine analog (fludarabine, cladribine, or pentostatin). A total of 293 patients were available for analysis of which 38% had acute leukemia or MDS, 18% had CML or another myeloproliferative disorder (MPD), 33% had CLL or lymphoma and 11% had a plasma cell disorder (PCD). The following transplant outcomes were analyzed: acute and chronic graft versus host disease (GVHD), non-relapse mortality (NRM), overall survival (OS) and event free survival (EFS).

Results: The number of URD-T performed as NST have increased for all disease categories. From 1995 to 1999, 24 transplants were performed for acute leukemia (AML, ALL and MDS); 13 for MPD; 25 for lymphoproliferative disorders (CLL and lymphoma) and 1 for PCD. In the year 2000 alone these increased to 56 transplants for acute leukemia, 53 for CLL or lymphoma, 30 for MPD and 20 for PCD. When compared to 7015 NMDP recipients of ablative allografts performed during the same time period, recipients of NST were older (52 vs. 32 years), were more likely to have undergone transplant in a disease phase other than CR1, CR2 or first Chronic Phase (79% vs. 51%) and were more commonly treated for NHL and AML. NST patients had received a prior transplant in 63% of cases, and 35% had a Karnofsky performance score (KPS) of &lt; 90 prior to transplant. The incidence of Grade II-IV acute GVHD for the whole group was 39% ± 5%. The 100 day and 1 year NRM rates were 20% ± 4% and 31% ± 5% respectively. Currently 83 patients are alive at a median of 985 days (range = 99–1825) with 77 patients free of progression. The 2 year OS and EFS rates are 33% ± 5% and 31% ± 5% respectively. On multivariate analysis favorable prognostic factors for OS were better HLA match, blood versus marrow stem cells and pre-transplant KPS ≥ 90%.

Hazard Ratio 95% Confidence Intervals HLA Matching Match 1 Potential Match 4.701 3.097–7.136 Mismatch 2.128 1.509–3.001 Karnofsky Performance Scale &lt; 90 1 ≥ 90 0.607 0.443–0.834 Stem Cell Source Peripheral Blood 1 Bone Marrow 1.602 1.151–2.229

Conclusions: URD-T with NST regimens are being performed more frequently, particularly in older patients. Although feasible and effective in a small fraction of patients, the procedure is still associated with significant morbidity and mortality. Factors relevant for outcomes after conventional myeloablative allografting (HLA match and performance status) remain important for outcomes after NST.