• T-cell prolymphocytic leukaemia;
  • stem cell transplantation;
  • autograft;
  • allograft;
  • alemtuzumab

T-cell prolymphocytic leukaemia (T-PLL) is a rare malignancy with an aggressive course and limited treatment options (Robak & Robak, 2007; Dungarwalla et al, 2008). The median survival in historical series is <1 year (Matutes et al, 1991). Only a minority of patients achieve a transient response to purine analogues (Mercieca et al, 1994). Used in two published series, the anti-CD52 monoclonal antibody alemtuzumab (Campath-1H) resulted in overall response rates between 51 and 76%, and complete responses (CR) between 39·5 and 60% (Dearden et al, 2001; Keating et al, 2002). Median survival remained short (7·5–9 months), but was 15–16 months in patients achieving CR. With approval from the research ethics and clinical research committees of the Royal Marsden NHS Trust, we investigated whether stem cell transplantation (SCT) after alemtuzumab can prolong survival in T-PLL.

Data were reviewed retrospectively from 28 patients in the UK (n = 16), Norway, France, Australia, New Zealand, Spain and Switzerland, treated between 1996 and 2008 with either autologous (n = 15) or allogeneic (n = 13) SCT after alemtuzumab. All centres followed the same protocol (Dearden et al, 2001) and all protocol-treated patients who underwent SCT were included in this study. Patient characteristics and treatment history are shown in Table I. Three non-responders to alemtuzumab achieved a good partial response (PR) after conditioning treatment, prior to SCT (Patients 15, 21 and 25, Table I).

Table I.   Characteristics and treatment history of patients receiving a stem cell transplant.
PatientType of SCTSexAge (years)Site of diseaseImmuno- phenotypePrior therapyBest response to prior therapyResponse to alemtuzumabConditioning regimenResponse after SCTRelapseDFS from SCT (months)Vital statusOS from alemtuzumab (months)
  1. SCT, stem cell transplant; allo, allograft; FIC, full -intensity conditioning; RIC, reduced-intensity conditioning; MUD, matched unrelated donor; Sib, sibling; M, male; F, female; B, blood; BM, bone marrow; Spl, spleen; Liv, liver; LN, lymph nodes; Pleu, pleural effusion; Asc, ascites; Chylo, chylothorax; Peri, periorbital oedema; CNS, central nervous system; DCF, pentostatin; CHOP, Cyclophosphamide, Doxorubicin, Vincristine, Prednisolone; Vapec-B, vincristine, doxorubicin, prednisolone, etoposide, cyclophosphamide and bleomycin; Sx, splenectomy; Chl, chlorambucil; R, rituximab; CR, complete response; PR, partial response; NR, no response (including stable disease); BEAC, BCNU, etoposide, cytarabine and cyclophosphamide; BEAM, BCNU, etoposide, cytarabine, and melphalan; Cyclo, cyclophosphamide; TBI, total body irradiation; Mel, melphalan; Etop, Etoposide; FDR, fludarabine; Alem, Alemtuzumab; Dexa, dexamethasone; DFS, disease-free survival; OS, overall survival.

  2. *Treated with combined alemtuzumab and pentostatin.

 3AutograftM63BM/Spl DCFNRCRCyclo/TBICRYes 56Died 89
 4AutograftM68B/BM/Spl/LNCD4+/CD8NONE CRMel/TBICRNo 81Alive 87
 5AutograftF55B/BM/Spl/Pleu/AscCD4/CD8+NONE CRMel/TBICRYes 39Died 65
 6AutograftF53B/BMCD4+/CD8+Vapec-B, Sx, DCFPRCR/CRMel/TBICRYes  9Died 55
 7AutograftM53B/BMCD4+/CD8+DCFPRCR/CRMel/TBICRYes 11Died 52
 8AutograftM62B/BM/SkinCD4+/CD8Chl/SteroidsNRCRMel/TBICRYes 28Died 48
 9AutograftF66B/BM/LarynxCD4+/CD8NONE CRCyclo/TBICRNo 45Alive 48
10AutograftM66B/BM/Spl/LN//Pleu/AscCD4+/CD8NONE CRBEAMCRYes 15Died 40
11AutograftF47B/BM/Spl/EyeCD4/CD8+NONE CRMel/TBICRYes 17Died 28
12AutograftF50B/BM/LN/SkinCD4/CD8+NONE CRMelCRYes 11Died 18
13AutograftF63B/BM/Spl/Liv/CNSCD4+/CD8DCFNRCR/PRBEAMCRYes  5Died 16
14AutograftM66B/BMCD4+/CD8NONE CRTBICRNo  8Alive 15
15AutograftM58B/BM/Spl/Liv/Skin/LNCD4+/CD8NONE NRCyclo/Etop/TBICRNo  2Died 14
16Allo RIC MUDM51B/BM/SkinCD4−/CD8+DCFNRPR*FDR/Mel/AlemCRNo110Alive120
17Allo FIC MUDF53B/LNCD4+/CD8+NONE CRCyclo/TBICRNo 37Alive 48
18Allo FIC MUDM56B/BM/SplCD4+/CD8NONE CRCyclo/TBICRNo 43Alive 48
19Allo FIC SibM39B/BMCD4/CD8+DCF, SxNRCRCyclo/TBICRYes 31Died 37
20Allo FIC MUDF41B/BM/Spl/LNCD4+/CD8+NONE CR*Cyclo/TBICRNo 28Alive 33
21Allo RIC SibM51B/BM/Sp/Liv/LNCD4/CD8+DCFNRNR*FDR/Mel/AlemCRYes 24Died 33
22Allo FIC MUDM51B/BM/Spl/LN/ChyloCD4+/CD8CHOP+RNRCR/PRCyclo/TBICRNo 21Died 32
23Allo RIC MUDF61B/BM/LN/Skin/PeriCD4+/CD8NONE CRFDR/Mel/AlemCRNo 25Alive 29
24Allo RIC SibM60B/Spl/LN/SkinCD4+/CD8NONE CR*FDR/Cyclo/AlemCRYes  5Died 18
25Allo FIC MUDM50B/BM/Spl/Liv/LNCD4/CD8+NONE NR*Dexa-BEAM/TBICRNo 11Died 18
26Allo FIC SibM56B/BM/SplCD4/CD8+NONE CRCyclo/TBICRYes  9Died 14
27Allo FIC SibM40B/BM/LNCD4/CD8+NONE CRCyclo/TBICRNo  2Died  7
28Allo FIC SibM57B/BM/SplCD4+/CD8+DCFPRCR*Cyclo/TBINENE  1Died  3

Clinical outcomes were compared against 23 patients with T-PLL who did not undergo SCT, retrospectively selected to include only those who achieved CR and survived >6 months after alemtuzumab treatment. Treated between 1992 and 2008, nine received alemtuzumab as first-line therapy and 14 received prior therapy: pentostatin alone (n = 7), other single agents (n = 4), or 2–3 prior therapies (n = 3).

The median age of the 15 autograft patients was 58 (range 43–68) years. Eight (53%) were male. At the time of SCT, 11 autograft patients were in their first CR after alemtuzumab, two were in a second CR and two were in a good PR. After autograft, all 15 patients achieved CR. There was one case of early treatment-related mortality (TRM), due to pneumonitis and multi-organ failure (Patient 15). Other toxicity included autoimmune haemolytic anaemia (Patient 10), streptococcal septicaemia and cutaneous herpes (Patient 13) and Escherichia coli with Klebsiella pneumoniae (Patient 2). Five patients remained alive and in CR, at 8, 45, 81, 107 and 115 months after the autograft. Nine patients relapsed, at a median of 15 months (range 5–56 months) and all died, 2–28 months after relapse. The median survival of the autograft patients, measured from the start of alemtuzumab treatment, was 52 months.

The 13 allograft patients were significantly younger than the autograft patients (P = 0·02), with a median age of 51 (range 39–61) years. Ten (77%) were male. At the time of SCT, 9 allograft patients were in their first CR after alemtuzumab and four were in a good PR. One non-assessable patient died 22 days post-SCT (Patient 28); all the others achieved CR. There were two cases of early and two of delayed TRM, including two sibling and two matched unrelated donor (MUD) allografts; all four patients had received full-intensity conditioning. These deaths were due to a fungal infection and subsequent multi-organ failure (Patient 28), refractory gut graft-versus-host disease (GvHD) and pseudomonal sepsis (Patient 27) and Epstein Barr virus (EBV)-associated post-transplant lymphoproliferative disease (PTLD) (Patients 22 and 25), with gastrointestinal and skin GvHD (Patient 25). Two other patients with EBV-positive PTLD relapsed and died of progressive disease (Patients 24 and 26). All the allogeneic SCT patients received ciclosporin and methotrexate as prophylaxis for GvHD. However, four patients developed GvHD, of whom three had full-intensity conditioning. Additional to the two fatalities reported above, Patient 17 had mild skin GvHD and Patient 16 had chronic, mild to moderate GvHD of gut, liver, skin and eyes continuing after 9 years. Other toxicity included haemorrhagic cystitis (Patient 18) and parvoviremia reactivation, with consequent red blood cell aplasia (Patient 20).

Five allograft patients remained alive and in CR at a follow-up from SCT of 25, 28, 37, 43 and 110 months; all had MUD allografts, two with reduced-intensity conditioning. Four patients relapsed and died of progressive disease, all after sibling allografts, two with full-intensity and two reduced-intensity conditioning (Table I). Patient 26 died of progressive disease 3 months after being reported minimal residual disease (MRD)-negative by polymerase chain reaction, probably due to disease harboured in ‘sanctuary’ sites (Dearden et al, 2001). The median survival of the allograft patients was 33 months.

Overall survival was similar in the autograft and allograft groups (P = 0·2, Figure 1A). Univariate analysis showed no significant association between survival and gender, age, extranodal disease, immunophenotype, prior treatment, response to alemtuzumab, whether in CR or PR prior to SCT, or conditioning regimen (data not shown). All 13 relapsed patients died of progressive disease. Five allograft and five autograft patients remained alive and in CR at a median follow-up from SCT of 81 and 37 months respectively. The median survival of all SCT patients was 48 months (Figure 1B).


Figure 1.  Overall survival in T-cell prolymphocytic leukaemia (measured from the start of alemtuzumab treatment). (A) Patients who received an autograft compared with those who received an allograft. (B) Patients who received a stem cell transplant after alemtuzumab compared with those who achieved a complete response after alemtuzumab and survived for at least 6 months, but who did not receive a stem cell transplant. (A statistical comparison was not considered appropriate as the two groups were not directly equivalent).

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The 23 non-SCT patients were similar to the SCT group in gender (70% males), disease characteristics, clinical presentation and prior treatment. Their median age was 64 (range 35–81) years, similar to the autograft group but older than the allograft group (P = 0·004) and the SCT patients as a whole (P = 0·007). However, their CR rate after alemtuzumab was higher than that of the SCT group. One non-SCT patient remained in CR 47 months after alemtuzumab treatment. Three further patients remained alive at 15, 19 and 34 months, all recently relapsed. Nineteen patients died from progressive disease. The median survival of the non-SCT patients was 20 months (Figure 1B), which compares favourably with previous reports, as described above. There was no association between age and survival in either group; thus the superior outcome after SCT was not accounted for by the age difference.

The evidence presented here suggests that SCT after alemtuzumab may provide benefit over alemtuzumab alone. Both autografts and allografts are associated with long-term survival in some patients.


  1. Top of page
  2. Acknowledgements
  3. Conflict of interest
  4. References

Monica Else was funded by the Arbib Foundation. We thank John Swansbury, Benet Nomdedeu, Robin Ireland, Béatrice Mahe, Anil Lakhani, Saad Rassam and all those other doctors who referred patients for this series. No further funding was involved.

Conflict of interest

  1. Top of page
  2. Acknowledgements
  3. Conflict of interest
  4. References

Claire Dearden received honoraria and research funding from Schering Health Care (UK). The remaining authors declare no conflict of interest.


  1. Top of page
  2. Acknowledgements
  3. Conflict of interest
  4. References
  • Dearden, C.E., Matutes, E., Cazin, B., Tjønnfjord, G.E., Parreira, A., Nomdedeu, B., Leoni, P., Clark, F.J., Radia, D., Rassam, S.M., Roques, T., Ketterer, N., Brito-Babapulle, V., Dyer, M.J. & Catovsky, D. (2001) High remission rate in T-cell prolymphocytic leukemia with CAMPATH-1H. Blood, 98, 17211726.
  • Dungarwalla, M., Matutes, E. & Dearden, C.E. (2008) Prolymphocytic leukaemia of B- and T-cell subtype: a state-of-the-art paper. European Journal of Haematology, 80, 469476.
  • Keating, M.J., Cazin, B., Coutré, S., Birhiray, R., Kovacsovics, T., Langer, W., Leber, B., Maughan, T., Rai, K., Tjønnfjord, G., Bekradda, M., Itzhaki, M. & Hérait, P. (2002) Campath-1H treatment of T-cell prolymphocytic leukemia in patients for whom at least one prior chemotherapy regimen has failed. Journal of Clinical Oncology, 20, 205213.
  • Matutes, E., Brito-Babapulle, V., Swansbury, J., Ellis, J., Morilla, R., Dearden, C., Sempere, A. & Catovsky, D. (1991) Clinical and laboratory features of 78 cases of T-prolymphocytic leukemia. Blood, 78, 32693274.
  • Mercieca, J., Matutes, E., Dearden, C., MacLennan, K. & Catovsky, D. (1994) The role of pentostatin in the treatment of T-cell malignancies: analysis of response rate in 145 patients according to disease subtype. Journal of Clinical Oncology, 12, 25882593.
  • Robak, T. & Robak, P. (2007) Current treatment options in prolymphocytic leukemia. Medical Science Monitor, 13, RA69RA80.