Successful mobilization and engraftment of PBSCs derived from donor cord blood cells after a previous allogeneic RIC single unrelated cord blood transplantation

To the editor:

We describe a successful salvage treatment with intensive chemotherapy and stem cell transplantation for a relapse of Hodgkin lymphoma (HL) after single umbilical cord blood transplantation with a reduced intensity-conditioning regimen (RIC).^1,2  The originality of this observation is the source of cells for the second transplantation; the grafted cells were obtained by the mobilization in the blood of stem cells (PBSCs) originating from the cord blood unit (CBU) used for the previous transplantation.

A 24-year-old patient was diagnosed with a nodular sclerosis classic HL (stage II Bb according to the Ann Arbor classification) in May 2007. A primary refractory disease was observed after 4 courses of adriamycin, bleomycin, vinblastine, and decarbazine (ABVD); 2 courses of mitoguazone, ifosfamide, vinorelbine, and etoposide plus rituximab (MINE-R); 2 courses of high-dose cytarabine (Ara-C), cisplatin, and dexamethasone (DHAP); and cervical irradiation (supplemental Table 1, available on the Blood Web site; see the Supplemental Materials link at the top of the online article). In August 2008, despite the availability of autologous stem cells and because of the chemotherapy refractoriness, we performed an allogeneic transplantation with RIC and a single unrelated CBU (6/6 HLA compatibility, 2.1 × 10⁷ nucleated cells [NC]/kg, and 0.5 × 10⁵ CD34⁺ cells/kg). RIC consisted of fludarabine (40 mg/m²/d on day −6 to day −2), cyclophosphamide (50 mg/kg/d on day −6), and a total body irradiation (2 Gy on day −1). Graft-versus-host disease (GVHD) prophylaxis associating oral mycophenolate mofetil (MMF; 1 g 3 times a day) and cyclosporine A (CsA; 4.5 mg/kg twice a day) was started on day −3. After thawing and washing, the viability of cells was 55%, the patient received 0.9 × 10⁷ NC/kg and 0.3 × 10⁵ CD34/kg. No grade > 2 conditioning-related toxicity was observed; the patient received G-CSF from day +22 to day +25 and was discharged at day +25 after the graft. Neutrophils were > 1000/L at day +40 and platelets > 50 000/L at day +52 after transplantation. Grade IIa acute (day +29) and chronic GVHD (eyes and mouth) were treated with appropriate doses of corticosteroids. MMF was stopped at day +30 and CsA at day +240. Complete remission (CR) was confirmed at 3 and 9 months after CBU transplantation. Full donor chimerism was documented by quantitative PCR³  on day +40 and sustained until relapse at 16 months. A relapse occurred in January 2010; the patient received 3 cycles of salvage chemotherapy (GVD) between April and July 2010 (supplemental Table 1).

PBSC CD34⁺ cells were stimulated with G-CSF (10 μg/kg/d for 5 days) after the second and third salvage cycles in July and August 2010 (Table 1). Apheresis collected 4.11 × 10⁶ CD34⁺ cells/kg; these cells originated from the previous transplanted CBU as shown by PCR analyses in blood and on the collected product (Figure 1). A second SCT, conditioned with carmustine, cytarabine, etoposide, and melphalan (BEAM), was performed in September 2010 with the injection of 2.79 × 10⁶ CD34⁺/kg (viability of 92%). The patient experienced transient grade 4 mucositis without any documented infection and rapidly recovered from aplasia with G-CSF support started on day +7; neutrophils were > 1G/L at day +11 and platelets > 50 G/L at day + 42 after the second transplantation. A sustained second CR has been maintained up to now and chimerism evaluations showed 100% derived-CBU cells at 1, 3, and 7 months.

This is the first report showing that, although CBUs contain 10 times fewer progenitor cells than bone marrow, CD34⁺ cell mobilization is feasible after CBU transplantation, allowing short- and long-term hematologic repopulation to occur by mobilized PBSCs issued from the original transplanted CBU.⁴