Feasibility of Second Autologous Peripheral Blood Stem Cell (PBSC) Collection Followed by a Second Cycle of High Dose Melphalan (HDM) in Patients Relapsing after an Initial Course of HDM for the Treatment of AL Amyloidosis.
Authors: Quillen Karen , Wright Daniel G. , Seldin David C. , Skinner Martha , Malek Karim , Finn Kathleen T. , Sanchorawala Vaishali 
Published: October 2019

Abstract
High-dose melphalan and autologous stem cell transplant (HDM/SCT) can induce complete hematologic responses (CR), defined as disappearance of the underlying monoclonal gammopathy from serum and urine by immunofixation electrophoresis, and of the clonal plasma cell dyscrasia by bone marrow immunohistochemistry, and extend survival in patients with AL amyloidosis. HDM/SCT results in a CR in 40% of patients, and leads to clinical improvements in organ function in >70% of those who achieve a CR. However, hematologic and clinical relapses occur in ~5% of patients who initially achieve a CR. Tandem cycles of HDM/SCT, for which sufficient PBSC collected during the initial cycle are saved for the second cycle of treatment, have been shown to achieve a higher ultimate CR rate of >60%. Among patients who do not achieve a CR following a single cycle of HDM/SCT, 30% nonetheless experience improvements in organ function. However, in this latter group, clinical improvements are not durable. Because there is limited experience with second PBSC collections in patients who have undergone prior myeloablative chemotherapy and because of the potential benefits of repeated cycles of HDM/SCT, we designed a study to explore the feasibility, and efficacy, of a second PBSC mobilization and collection followed by a second cycle of HDM/SCT in patients who relapse after initially responding to a first cycle of HDM/SCT.
Results: Five patients, median age 52 (range 43–59), M:F 1.5:1.0, who had achieved hematologic and clinical responses after an initial cycle of HDM/SCT, were treated with a second cycle of HDM/SCT when a hematologic and/or clinical relapse occurred after a median time interval of 39 mo.(range 16–63 mo.). After G-CSF mobilization a mean of 5.2 million CD34 cells/kg was collected in a median of 3 days (range 2–4 days). The yields were not significantly different from those of the first cycle of HDM/SCT. Engraftment occurred at a median of 10 days for neutrophils, and 13 days for platelets (two days without platelet transfusion support); this engraftment timing is similar to that following initial transplants (11 and 12 days respectively). There was no treatment-related mortality, but toxicity was moderate; all patients experienced grade III/IV non-hematologic toxicities. For the 3 patients evaluable at 1 year, no hematologic CR was observed; these patients expired at 38, 37 and 15 mo. Two patients are alive at 5 and 11 mo. post transplant.
Conclusion: Patients with AL amyloidosis who experience a hematologic or clinical relapse after responding to an initial course of HDM/SCT can successfully be re-mobilized, and undergo a second cycle of HDM/SCT, with prompt hematopoietic recovery. Clinical benefits of second cycles of HDM/SCT in this setting have yet to be determined.
Patient data
prior Rx CD34 yield #1/#2 (10E6 cells/kg) HDM #1/#2 (melphalan dose mg/m2) Days to WBC eng #1/#2 Days to PLT eng #1/#2 CR#1/CR#2 Survival (mo.) #1/#2 refer to first/second transplant 1 none 8.0/4.1 200/200 9/11 9/12 yes/no 38 2 M/P x2 8.8/7.7 200/200 11/10 12/34 no/no 37 3 VAD x3 7.9/4.6 200/140 11/10 17/13 no/no 15 4 M/P x2 5.9/6.2 200/200 9/9 12/24 no/? alive at 11 mo. 5 none 4.3/3.4 200/140 11/10 11/11 no/? alive at 5 mo.