Allogeneic stem cell transplantation after reduced-intensity conditioning in a patient with T-cell prolymphocytic leukemia: graft-versus-tumor effect and long-term remission

T-cell prolymphocytic leukemia (T-PLL) is a rare aggressive lymphoid malignancy associated with a short median patient survival and poor response to chemotherapy.1, 2, 3 Currently, there is no standard treatment for T-PLL, and disease progression ultimately occurs in most cases. Allogeneic stem cell transplantation (allo-SCT) with myeloablative conditioning has been used in a few cases with T-PLL.2, 4, 5, 6 However, treatment-related mortality is significant with this kind of conditioning, precluding its use in elderly or heavily pre-treated patients. However, reduced-intensity conditioning (RIC) allo-SCT has been shown to be associated with decreased transplant-related toxicities while preserving the graft-versus-tumor effect (GVT).7 We report the case of a T-PLL patient successfully treated with RIC allo-SCT.

In January 2002, a 30-year-old male with a previous history of type 1 diabetes, presented with fever, poor general condition and abdominal pain. Physical examination revealed liver enlargement, without peripheral adenopathy. The white blood-cell count was 57 × 109/l with 73% abnormal lymphocytes. Platelets were low at 48 × 109/l. Bone marrow aspirate showed 52% abnormal T-lymphocytes compatible with a diagnosis of T-PLL. Flow cytometric analysis of bone marrow lymphocytes revealed a characteristic post-thymic T-cell phenotype (CD2+, CD5+, CD7+, CD8+, HLA DR+, CD25−). CT-scan showed homogenous liver enlargement and signs of lung infection. Cytogenetic analysis of the abnormal T lymphocytes was normal.

The patient was initially treated with four induction courses of CHOP chemotherapy (doxorubicine 50 mg/m2, cyclophosphamide 750 mg/m2, vincristine 1.4 mg/m2, and prednisone 1 mg/kg/day for 5 days), followed by high-dose melphalan (140 mg/m2) and autologous G-CSF-mobilized peripheral blood stem cell support. Complete remission was achieved 1 month after autologous transplantation, as ascertained by a normal CT-scan and normal bone marrow aspirate. Unfortunately, relapse in bone marrow occurred 2 months after high-dose melphalan, with 10% infiltrating abnormal T-cell lymphocytes.

At this stage, RIC allo-SCT from his HLA-matched sister was performed, with a preparative regimen including fludarabine 150 mg/m2, busulfan 8 and 2.5 mg/kg antithymocyte globuline (ATG; Genzyme, Paris, France). No grade 3–4 toxicities were observed during conditioning. ANC>0.5 × 109/l and platelets>20 × 109/l were achieved by day 23 and day 16 after allo-SCT, respectively. Cyclosporine A and mycophenolate mofetil were used for graft-versus-host disease (GVHD) prophylaxis. At day 32 after allo-SCT, the patient was diagnosed with grade 3 acute GVHD (gut and skin involvement), controlled with corticosteroids (2 mg/kg/day) and ATG (10 mg/kg total dose). Significantly, concomitant to acute GVHD onset, the bone marrow aspirate was found to be entirely normal. Subsequently, the patient developed progressive extensive chronic GVHD (skin, mucosa and liver involvement) necessitating multiple lines of immunosuppressive therapy, to effect control. With a follow-up of 38 months after allo-SCT, the patient is still alive in complete remission, but with signs of moderate chronic GVHD (prednisone 10 mg/day; ocular sicca syndrome, and moderate liver abnormalities).

T-PLL is an incurable lymphoid malignancy with a poor median survival (7.5 months).1, 2, 3 Allogeneic stem cell transplantation is not a classical treatment approach for patients with T-PLL, and only eight cases have been reported to date (Table 1). Among these eight cases, three patients were treated in a so-called non-myeloablative setting.2, 4, 5, 6, 8 The first reported case of T-PLL treated with allo-SCT received a standard myeloablative preparative regimen. In this case, a GVT effect was likely to have occurred since the patient experienced both acute and chronic GVHD and was still in complete remission 3 years after allo-SCT.4 Among the other four cases of T-PLL who received a standard myeloablative allo-SCT, three were reported to be already in complete remission at the time of allo-SCT with various follow-up periods (9, 16 and 24 months).2, 5, 6 One case of transplant-related mortality occurred 3 weeks after allo-SCT.2 Acute or chronic GVHD were not reported. Since the median age at diagnosis of T-PLL is around 70 years, a RIC regimen prior to allo-SCT is likely to represent the only preparative therapy for patients with an HLA-matched donor. Three cases of RIC allo-SCT for T-PLL have been reported to date.2, 8 None of these cases was able to truly document a genuine GVT effect and long-term sustained remission, as one patient died from disease relapse 5 months after RIC allo-SCT,8 and another had a follow-up period of only 2 months. The third case had 11 months of follow-up but was already in complete remission after high-dose chemotherapy (BEAM regimen) and autologous transplantation performed prior to RIC allo-SCT.2 In this regard, it is noteworthy that high-dose chemotherapy has already been shown to be able to induce complete remissions in some cases of T-PLL, lasting up to 15 months.2 The case presented here strongly suggests the existence of a potent GVT effect in T-PLL, since allo-SCT was performed with evidence of disease relapse, while complete remission was achieved concomitantly with GVHD onset. The fludarabine contained in the reduced intensity preparative regimen may have played a role in disease response. However, this is unlikely given the aggressiveness of the disease in this patient (failure of previous chemotherapy, and relapse 2 months after autologous transplantation).

Table 1 Reported cases of patients with T-PLL who underwent allo-SCT

This case suggests that RIC allo-SCT is a potentially curative therapeutic option for T-PLL patients. Given the relatively low incidence of transplant-related mortality associated with the use of nonmyeloablative and less toxic preparative regimens,7 we conclude that if an HLA-matched sibling is identified, RIC allo-SCT should be considered, even in elderly or heavily pre-treated patients presenting with this incurable disease.


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de Lavallade, H., Faucher, C., Fürst, S. et al. Allogeneic stem cell transplantation after reduced-intensity conditioning in a patient with T-cell prolymphocytic leukemia: graft-versus-tumor effect and long-term remission. Bone Marrow Transplant 37, 709–710 (2006).

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