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Patients in complete clinical remission after myeloablative allogeneic stem cell transplantation (allo-SCT) were enrolled in a longitudinal study to assess the predictive value of molecular monitoring. Using polymerase chain reaction (PCR) for immunoglobulin gene rearrangements it was possible to generate a clone-specific molecular marker in 48 of 70 patients. Of these 48 patients, 16 (33%) attained durable PCR-negativity after transplantation, whereas 13 (27%) remained persistently PCR-positive and 19 (40%) showed a mixed pattern. The cumulative risk of relapse at 5 years was 0% for PCR-negative patients, 33% for PCR-mixed patients, and 100% for PCR-positive patients. Within the group studied it was not possible to identify any clinical feature predictive of durable PCR-negativity. We believe that these findings could prompt the design of prospective studies to evaluate if the treatment of molecular disease can extend remission duration and survival.

CD34+ selection of peripheral blood progenitor cells (PBPC) was used in Multiple Myeloma (MM) in an attempt to reduce tumor cell contamination and relapse rate. From May 1995 to November 1999, 127 patients from 17 EBMT centers with newly diagnosed advanced MM were entered into a phase III trial. Responders to 3 cycles of VAD were randomized to receive either CD34+ selected (arm A) or unselected PBPC (arm B) following myeloablative conditioning treatment. PBPC were harvested following mobilization with cyclophosphamide 4g/m² and G-CSF (Filgrastim, AMGEN, Europe). Conditioning regimen in both arms was TBI and high dose melphalan 140 mg/m². CD34+ cell selection was performed in arm A using the CellPro Ceprate-SC device. The analysis concerns the 111 patients who were transplanted (56 arm A and 55 arm B). The median follow-up at the time of the analysis was 65 months. CD34+ selection resulted in a median purity of 87% and a yield of 50%. Molecular analysis showed a median tumor cell depletion of 2.0 log (range 0.3–85.5). The median number of CD34+ cells reinfused/kg was 5.8 x 106 (1.42–50.4) in arm A and 7.4x106 (1.85–99.2) in arm B. The median time to neutrophil engraftment (ANC >0.5x109/l) was 10 days (range 8–14) in arm A and 10 days (range 8–21) in arm B. The median time to platelet engraftment (plts>20 x 109/l) was 11 days (range 5–26) in arm A and 9 days (range 5–42) in arm B (p=0.005). One patient died before platelets engraftment in arm A. Twelve patients experienced at least one episode of serious infection (total episodes =17) before day 100 in arm A compared to 3 patients (total episodes = 6) in arm B (p=0.02). For 3 patients in arm A, these infections were fatal (including the patient who died before time to platelet engraftment). There was no significant difference in CR rate at 1 year as defined by EBMT/IBMTR/ABMTR criteria (27% in arm A and 20% in arm B). The 5 year overall survival (OS) was 51% in arm A and 45% in arm B (p=0.80). The 5 year event free survival was 20% in arm A and 18% in arm B (p=0.45). The increased incidence of severe infections in the CD34+ selected arm in the early post transplant may be due to impaired immune reconstitution. Thus, no long term clinical benefit is obtained by CD34+ selection despite significant tumor cell reduction.

A simple in vitro method has been developed for the assessment of ineffective erythropoiesis by measuring the release of heme from a labeled cohort of erythroblasts in short-term suspension culture. The release of labeled heme was shown to correlate with the death of erythroblasts in culture determined by cell counting. Heme release was markedly increased in conditions where there is known to be excessive ineffective erythropoiesis, while in hematologic disorders where ineffective erythropoiesis is thought to be normal, heme release was within the normal range.