To the Editor: Treatment for relapsed ⁄ refractory Hodgkin’s lymphoma (HL) remains difficult. Approximately 80% of patients with HL are cured with chemotherapy with or without radiotherapy (1). Relapsing patients are treated with autologous hematopoietic stem cell transplantation (HSCT) (2). A subgroup of patients, resistant to this type of treatment, is eligible for allogeneic HSCT (3). High rates of treatment related mortality (TRM), up to 50– 60%, have been reported with myeloablative conditioning (4). Therefore, allogeneic HSCT is not an approach used widely. Reduced intensity conditioning (RIC) for HL is currently being evaluated. The rationale for RIC-HSCT is exploiting a putative graft-versus-lymphoma (GvL) effect (5). Several groups have reported results on RIC allogeneic HSCT in HL and have shown decreased TRM rates (6–8). Comparisons are difficult, since RIC regimens varied. Only few patients have been treated with HSCT from unrelated donors. The only published series using alemtuzumab has shown a 34% TRM for unrelated donors with a high rate of viral infections (8, 9). A recent publication from the European group for blood and marrow transplantation (EBMT) comparing standard conditioning to RIC showed a disappointing progression free survival (PFS) of only 20% and overall survival of 28% at 5 yr (10). Variable results are most likely due to different proportions of chemorefractory patients. Thus, the optimal transplantation approach for allogeneic HSCT in HL has not been defined. We report a small cohort of eight consecutive patients with refractory or multiply relapsed HL, all with nodular sclerosis histology, relapsing after autologous ⁄ syngeneic HSCT, receiving an allogeneic HSCT, using fludarabine (5 · 30 mg ⁄m) – melphalan (2 · 70 mg ⁄m) – ATG (ATG Fresenius 5 · 5 mg ⁄kg) RIC with in vitro T-cell depletion by Campath-1H and T-cell add-back on the day after transplantation (130 · 10 CD3 cells ⁄kg (11), for related donors or 0.35 · 10 CD3 cells ⁄kg for unrelated donors). Immunosuppression was with cyclosporine and mycophenolate. All patients gave their written informed consent for data analysis and reporting. The goal was to decrease incidence and severity of acute and chronic graft-versus-host disease (GvHD) without loosing the GvL effect by providing risk-adapted T-cell immunotherapy (11). Two patients were transplanted without T-cell depletion (unique patient number [UPN] 250 and 263) for logistic reasons. In case of mixed chimerism or persistent disease on day + 100, incremental donor lymphocyte infusions (DLI) were started at a dose of 1 · 10 CD3 cells ⁄kg followed every 6–8 wk by increments of half a log CD3 cells ⁄kg until complete chimerism and complete remission (CR) occurred or until the occurrence of acute GvHD grade ‡II. Transplant and patients characteristics as well as hematological recovery data are presented in Table 1. Median number of prior lines of treatment was four (4–6), interval from diagnosis to HSCT was 52 (26–99) months. All patients engrafted, median time to neutrophil and platelet (>50 G ⁄L) recovery was 14.5 (10–17) d and 12 (10–14) d, respectively. All patients had >90% donor chimerism at day + 100. Median follow up of surviving patients is 3.4 yr (1.8–6.8). Two patients with chemoresistant disease died due to disease relapse or progression (on day + 454 and +76). The six other patients are alive, five free of disease and one currently undergoing salvage chemotherapy after being in CR for 517 d after DLI (Table 1, Fig. 1).Only one patient who had received a non-T-cell depleted graft developed aGvHD (grade II) after transplant and before DLI. Five of the six patients transplanted with a T-cell depleted graft received DLI according to protocol (Table 1). Acute GvHD developed in four of these patients, one with grade I, two with grade II and one with grade III. Acute GvHD progressed to extensive chronic GvHD in three patients and to limited in one. Of the six surviving patients two are currently off immunosuppression. Five patients received DLI for mixed chimerism or persistent disease, three on day + 100 [all in CR at last follow-up (FU)] and two at a later date. The estimated 3 yr OS was 75% (95% CI 45–100%). The present small series suggests that a transplant regimen based on fludarabine-melphalan and ATG with a T-cell depleted graft, immediate graded T-cell add-back and early DLI for residual disease or mixed chimerism allows for full engraftment with low TRM. Other similar series were associated with low (12) or considerable TRM of 15–25% (7–14). We may be getting closer to the goal of low TRM doi:10.1111/j.1600-0609.2009.01282.x European Journal of Haematology 83 (273–275)
[1]
S. Mackinnon,et al.
Superiority of reduced-intensity allogeneic transplantation over conventional treatment for relapse of Hodgkin's lymphoma following autologous stem cell transplantation
,
2008,
Bone Marrow Transplantation.
[2]
M. Munsell,et al.
Fludarabine-melphalan as a preparative regimen for reduced-intensity conditioning allogeneic stem cell transplantation in relapsed and refractory Hodgkin’s lymphoma: the updated M.D. Anderson Cancer Center experience
,
2008,
Haematologica.
[3]
N. Schmitz,et al.
Reduced-intensity conditioning compared with conventional allogeneic stem-cell transplantation in relapsed or refractory Hodgkin's lymphoma: an analysis from the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation.
,
2008,
Journal of clinical oncology : official journal of the American Society of Clinical Oncology.
[4]
A. Santoro,et al.
Reduced‐intensity allogeneic transplantation in patients with refractory or progressive Hodgkin's disease after high‐dose chemotherapy and autologous stem cell infusion
,
2007,
European journal of haematology.
[5]
J. Garcia-conde,et al.
Nonmyeloablative stem cell transplantation is an effective therapy for refractory or relapsed hodgkin lymphoma: results of a spanish prospective cooperative protocol.
,
2006,
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.
[6]
B. Chapuis,et al.
Can only partial T-cell depletion of the graft before hematopoietic stem cell transplantation mitigate graft-versus-host disease while preserving a graft-versus-leukemia reaction? A prospective phase II study.
,
2006,
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.
[7]
C. Craddock,et al.
Clinical evidence of a graft-versus-Hodgkin's-lymphoma effect after reduced-intensity allogeneic transplantation
,
2005,
The Lancet.
[8]
N. Ueno,et al.
Reduced-intensity allogeneic stem cell transplantation in relapsed and refractory Hodgkin's disease: low transplant-related mortality and impact of intensity of conditioning regimen
,
2005,
Bone Marrow Transplantation.
[9]
D. Ritchie,et al.
Graft-versus-lymphoma effects: clinical review, policy proposals, and immunobiology.
,
2004,
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.
[10]
A. Romanelli,et al.
Autografting followed by nonmyeloablative immunosuppressive chemotherapy and allogeneic peripheral-blood hematopoietic stem-cell transplantation as treatment of resistant Hodgkin's disease and non-Hodgkin's lymphoma.
,
2000,
Journal of clinical oncology : official journal of the American Society of Clinical Oncology.
[11]
D. Neuberg,et al.
Assessment of the stanford V regimen and consolidative radiotherapy for bulky and advanced Hodgkin's disease: Eastern Cooperative Oncology Group pilot study E1492.
,
2000,
Journal of clinical oncology : official journal of the American Society of Clinical Oncology.
[12]
F. Mandelli,et al.
Conventional salvage chemotherapy vs. high-dose therapy with autografting for recurrent or refractory Hodgkin's disease patients
,
2000,
Annals of Hematology.
[13]
A. Fielding,et al.
Allogeneic bone marrow transplant is not better than autologous transplant for patients with relapsed Hodgkin's disease. European Group for Blood and Bone Marrow Transplantation.
,
1996,
Journal of clinical oncology : official journal of the American Society of Clinical Oncology.
[14]
S. Crawford,et al.
Allogeneic, syngeneic, and autologous marrow transplantation for Hodgkin's disease: the 21-year Seattle experience.
,
1993,
Journal of clinical oncology : official journal of the American Society of Clinical Oncology.