Cutaneous T-cell Lymphomas: History
Please note this is an old version of this entry, which may differ significantly from the current revision.
Subjects: Others
Contributor:

Although various anti-cutaneous T cell lymphoma (CTCL) therapies are available for clinical use, appropriate chemotherapy lines for the treatment of CTCLs have yet to be established. Therefore, to date, various clinical trials for the treatment of advanced CTCLs are ongoing. In this review, we evaluate the therapeutic options that are available in clinical practice, for treatment of early- and advanced-stage CTCLs (targeted therapies, histone deacetylase (HDAC) inhibitors, retinoids, interferons, cytotoxic drugs, etc.). We also examine clinical trials of novel regimens for the treatment of CTCLs.

  • CTCL
  • topical formulation
  • bexarotene
  • targeted therapy
  • interferon

1. Surface Molecular-targeted Therapy for Advanced CTCLs

Among surface molecular-targeted therapies, mogamulizumab, brentuximab vedotin, denileukin diftitox, alemtuzumab, and pembrolizumab are recommended by the 2020 NCCN guidelines for the treatment of primary cutaneous lymphomas [1] (Table 1).

Table 1. The efficacy of systemic formulations for treatment of CTCLs.

Protocol

ORR (%)

CR (%)

PR (%)

PFS

Most Common AEs (%)

Most Common SAEs (%)

Mogamulizumab

28

   

7.7 months

infusion reaction (32%)

pyrexia (4%)

Brentuximab vedotin

56.3

     

neuropathy (50%)

neuropathy (5%)

Denileukin diftitox

44

10

34

>2 years

fatigue (12%)

capillary leak syndrome (2%)

Pembrolizumab

37.5

8.3

29.2

     

Alemtuzumab

51.1

17.9

33.3

3.4 months

 

severe infectious AEs (62%)

 High-dose IFN-a2a

29

4

25

     

IFN-a2a plus PUVA

80.6

74.6

6

32 months

   

IFN-a2b with PUVA

93

73

20

>2 years

   

IFN-g

60

   

>170 days

flu-like illness (100%)

 

Bexarotene

45

     

hypertriglyceridemia

hyperlipidemia

Vorinostat

29.5

   

9.8 months

diarrhea (49%)

thrombocytopenia (5%)

Romidepsin

33.8

5.6

28.2

13.7 months

nausea (73.2%)

 

Quisinostat

24

   

2.8–6.9 months

nausea, diarrhea (23%)

hypertension (11.5%)

Pralatrexate

44.8

3.4

41.4

 

 mucositis (48%)

mucositis (17%)

Gemcitabine

75

21.8

53.1

10 months

 

 

Pegylated liposomal doxorubicin

56

20

36

5 months

 

 

PFS: progress free survival, SAE: severe adverse event

2. Immunomodulatory Reagents: Interferon (IFN), Bexarotene, Etoposide

Immunomodulatory reagents have been used classically for the treatment of CTCLs. Among these reagents, IFN and bexarotene recently have been investigated for their immunomodulatory effects on the CTCL tumor microenvironment [2][3][4]. These reports suggest the possible utility of combination therapies for CTCL, such as IFN-α2a in combination with psoralen with ultraviolet light A (PUVA), low-dose methotrexate, or retinoid [5][6][7], or bexarotene plus phototherapy [8][9]. Preclinical findings suggest that more immunomodulatory reagent-based combination therapies will be established in the future.

3. HDAC Inhibitors (Vorinostat, Romidepsin, Quisinostat)

HDAC inhibition restores histone acetylation in CTCL cells to normal levels, thereby activating gene expression and leading to the induction of growth arrest, cellular differentiation, and apoptosis [10][11]. Indeed, various HDAC inhibitors have been investigated for the treatment of CTCL. Among these compounds, vorinostat has been approved by the FDA for the treatment of advanced CTCL. Initial clinical trial reports found an ORR of 29.5% for patients with CTCL at Stage IIB or higher [64]. Median time to progression was 9.8 months for responders at Stage IIB or higher. The most common drug-related AEs were diarrhea (49%), fatigue (46%), nausea (43%), and anorexia (26%), and the most common SAEs were fatigue (5%), pulmonary embolism (5%), thrombocytopenia (5%), and nausea (4%). Notably, in another clinical trial, the median PFS with vorinostat was 3.1 months (95% CI: 2.9–4.1 months) for relapsed CTCL, which is a value that is inferior to that obtained with mogamulizumab (HR 0.53; 95% CI 0.41–0.69; stratified log-rank p < 0.0001) [12].

Romidepsin is an another potent HDAC inhibitor that is isolated from the bacterium Chromobacterium violaceum; this compound has been approved by the FDA for the treatment of CTCL and peripheral T cell lymphoma (PTCL) [13]. The first phase II multi-institutional trial of romidepsin monotherapy for CTCL showed an ORR of 33.8% (95% CI: 23–46%) with four cases of CR (5.6%) and 20 cases of PR (28.2%), and the median DOR was 13.7 months. Safety profiles included nausea (73.2%), fatigue (57.7%), vomiting (26.8%), transient thrombocytopenia (56.3%), granulocytopenia (50.7%), anemia (52.1%), and leukopenia (42.3%).

Quisinostat is a second-generation pan-HDAC inhibitor with a broad spectrum of preclinical anti-tumor activity against various hematological malignancies, including CTCL [14]. Recently, the results of a phase II multicenter trial of oral quisinostat in 26 patients with previously treated MF or SS were reported [66]. The ORR was 24% as assessed by cases with >50% reduction of mSWAT score; the DOR in skin ranged from 2.8 to 6.9 months. The most common drug-related AEs were nausea, diarrhea (23%), asthenia (15%), hypertension (8%), thrombocytopenia (11%), and vomiting (11%) [15]. The incidence of SAEs was 11.5%, including single cases of hypertension, lethargy, and pruritus. Overall, quisinostat appears to be better tolerated than first-generation HDAC inhibitors such as vorinostat or romidepsin.

4. Anti-Metabolic Drugs: Pralatrexate, Methotrexate (MTX)

Paralatrexate is an antineoplastic folate analog similar to MTX; both compounds exhibit high affinity for the reduced folate carrier type-1 oncoprotein [16][17][18]. Paralatrexate inhibits dihydrofolate reductase, thereby disrupting DNA synthesis and leading to the induction of cytotoxicity against CTCL cells [19]. In a preclinical study, paralatrexate showed superior activity against human lymphoma cells compared to MTX [20]. A phase I dose de-escalation study for relapsed or refractory CTCL suggested that the ORR of pralatrexate was 45% (13/29) (95% CI: 26.4–64.3%) with 1 case of CR and 12 of PR [21]. The most common AEs were mucositis (48%), fatigue (41%), nausea (31%), edema (28%), epistaxia (21%), pyrexia (21%), anorexia (21%), and skin toxicity (21%). The most common SAEs were mucositis (17%) and leukopenia (3%). More recently, Duvic et al. reported the results of a phase I/II open-label, multicenter clinical trial for pralatrexate (15 mg/m2) plus bexarotene (150 mg/m2) combination therapy for relapsed or refractory CTCL [22]. The ORR was 60% (18/31), including four cases with CR and 14 with PR; the DOR for CR patients was 9.0 to 28.3 months. The median PFS was 12.8 months [23]. The most common AEs with this combination therapy were stomatitis (65%), hypertriglyceridemia (56%), fatigue (44%), nausea (32%), neutropenia (32%), central hypothyroidism (24%), and anemia (24%) [24]. The most common SAEs were neutropenia (35%), hypertriglyceridemia (29%), and stomatitis (21%) [25] Overall, pralatrexate is effective for relapsed or refractory CTCL with acceptable toxicity, especially when administered in combination with bexarotene.

MTX is an analog of folic acid that has been used classically (since 1964) for the treatment of MF [26][27]. In addition, a retrospective study of low-dose MTX for the treatment of patients with MF has been conducted [28]. The ORR of low-dose MTX for MF was 30.4% (21/69), including seven cases with CR and 14 with PR [28]. Notably, most of the responding patients had early-stage (patch or plaque) MF, with the exception of one patient with tumor-stage disease [28]. In addition, the results of a multicenter observational study of MTX for the treatment of patients with MF found an ORR of 70.9% (56/79) [22]. Those authors concluded that the response of subjects with MF to MTX depended on the dose of MTX and the stage of MF [22]. Overall, low-dose MTX monotherapy is well-tolerated and effective, especially for MF, notably in early-stage disease.

5. Miscellaneous Therapies Preferred Systemic Therapies: Gemcitabine, Pegylated Liposomal Doxorubicin, and Extracorporeal Photopheresis (ECP)

As described above, the NCCN guidelines for primary cutaneous lymphomas suggest a systemic therapy option for the treatment of advanced MF/SS [1]. Among cytotoxic drugs for CTCL, gemcitabine and pegylated liposomal doxorubicin are recommended as SYST-CAT B together with brentuximab vedotin and pralatrexate [1]. Gemcitabine is a pyrimidine antimetabolite that has been used for the treatment of advanced CTCL. Two phase II studies have been reported. The first found an ORR of gemcitabine monotherapy of 75% (24/32) for CTCL (including MF, peripheral T cell lymphoma, and SS), with seven cases of CR, and 73% (19/26) for MF with six cases of CR; the median PFS for CTCL was 10 months [29]. In the second report, the ORR of gemcitabine monotherapy was 68% (17/25) for CTCL, with three cases of CR, and the median PFS for CTCL was 4.1 months [30]. Pegylated liposomal doxorubicin, which is doxorubicin encapsulated in liposomes that leads to decreased cardiotoxicity and nephrotoxicity, is recommended for the treatment of CTCLs in the NCCN guideline as SYST-CAT B [1]. A prospective multicenter study found an ORR of pegylated liposomal doxorubicin for MF/SS of 56% (14/25), with five CR (20%), and a median PFS of 5 months [31]. Although CHOP is the standard regimen in patients with non-Hodgkin’s lymphoma including CTCL [32], the DOR is limited compared to surface molecular-targeted therapy such as brentuximab vedotin [33]. Overall, these cytotoxic drugs could be other options for the treatment of CTCL, although the incident ratio of SAEs was high (36–40%) [31][32]. Etoposide, chlorambucil, cyclophosphamide, pentostatin, temozolomide, and bortezomib are also recommended in the NCCN guidelines as useful drugs under certain circumstances [1].

ECP is a leukapheresis-based therapy that exposes the isolated lymphocytes from peripheral blood to 8-methoxypsoralen and ultraviolet A radiation, and it has been used for the treatment of CTCL as SYST-CAT A[34]. The ORR of ECP for SS has been found to be 55.7% with a CR rate of 17.6% [35]. Notably, since ECP can be combined with other systemic therapies such as IFNs and bexarotene [36], ECP should be considered for the treatment of CTCL, although the availability of ECP might be limited.

This entry is adapted from the peer-reviewed paper 10.3390/pharmaceutics13020200

References

  1. Mehta-Shah, N.; Horwitz, S.M.; Ansell, S.; Ai, W.Z.; Barnes, J.; Barta, S.K.; Clemens, M.W.; Dogan, A.; Fisher, K.; Goodman, A.M.; et al. NCCN Guidelines Insights: Primary Cutaneous Lymphomas, Version 2.2020. J. Natl. Compr. Cancer Netw. 2020, 18, 522–536.
  2. Furudate, S.; Fujimura, T.; Kakizaki, A.; Hidaka, T.; Asano, M.; Aiba, S. Tumor-associated M2 macrophages in mycosis fun-goides aquired immunomodulatory function by interferon alpha and interferon gamma. J. Dermatol. Sci. 2016, 83, 182–189.
  3. Goteri, G.; Rupoli, S.; Campanati, A.; Zizzi, A.; Picardi, P.; Cardelli, M.; Giantomassi, F.; Canafoglia, L.; Marchegiani, F.; Mozzicafreddo, G.; et al. Serum and tissue CTACK/CCL27 chemokine levels in early mycosis fungoides may be correlated with disease-free survival following treatment with interferon alfa and psoralen plus ultraviolet A therapy. Br. J. Dermatol. 2012, 166, 948–952, doi:10.1111/j.1365-2133.2012.10818.x.
  4. McGinnis, K.S.; Junkins-Hopkins, J.M.; Crawford, G.; Shapiro, M.; Rook, A.H.; Vittorio, C.C. Low-dose oral bexarotene in combination with low-dose interferon alfa in the treatment of cutaneous T-cell lymphoma: Clinical synergism and possible immunologic mechanisms. J. Am. Acad. Dermatol. 2004, 50, 375–379, doi:10.1016/j.jaad.2003.10.669.
  5. Chiarion-Sileni, V.; Bononi, A.; Fornasa, C.V.; Soraru, M.; Alaibac, M.; Ferrazzi, E.; Redelotti, R.; Peserico, A.; Monfardini, S.; Salvagno, L. Phase II trial of interferon-alpha-2a plus psolaren with ultraviolet light A in patients with cutaneous T-cell lym-phoma. Cancer 2002, 95, 569–575, doi:10.1002/cncr.10706.
  6. Olisova, O.Y.; Megna, M.; Grekova, E.V.; Zaslavsky, D.; Gorenkova, L.G.; Sidikov, A.A.; Timoshchuk, E.A. PUVA and inter-feron α2b combined therapy for patients with mycosis fungoides at different stages of the disease: A seven-year retrospective study in Russia. J. Eur. Acad. Dermatol. Venereol. 2019, 33, e72–e74, doi:10.1111/jdv.15212.
  7. Avilés, A.; Neri, N.; Fernandez-Diez, J.; Silva, L.; Nambo, M.-J. Interferon and low doses of methotrexate versus interferon and retinoids in the treatment of refractory/relapsed cutaneous T-cell lymphoma. Hematology 2015, 20, 538–542, doi:10.1179/1607845415y.0000000002.
  8. Morita, A.; Tateishi, C.; Muramatsu, S.; Kubo, R.; Yonezawa, E.; Kato, H.; Nishida, E.; Tsuruta, D. Efficacy and safety of bex-arotene combined with photo(chemo)therapy for cutaneous T-cell lymphoma. J. Dermatol. 2020, 47, 443–451, doi:10.1111/1346-8138.15310.
  9. Fujimura, T.; Sato, Y.; Tanita, K.; Amagai, R.; Shimauchi, T.; Ogata, D.; Fukushima, S.; Miyashita, A.; Fujisawa, Y.; Kam-bayashi, Y.; et al. Case series of cutaneous T-cell lymphomas treated with bexarotene-based therapy. J. Dermatol. 2020, 47, 636–640, doi:10.1111/1346-8138.15322.
  10. Olsen, E.A.; Kim, Y.H.; Kuzel, T.M.; Pacheco, T.R.; Foss, F.M.; Parker, S.; Frankel, S.R.; Chen, C.; Ricker, J.L.; Arduino, J.M.; et al. Phase IIB Multicenter Trial of Vorinostat in Patients with Persistent, Progressive, or Treatment Refractory Cutaneous T-Cell Lymphoma. J. Clin. Oncol. 2007, 25, 3109–3115, doi:10.1200/jco.2006.10.2434.
  11. Piekarz, R.L.; Frye, R.; Turner, M.; Wright, J.J.; Allen, S.L.; Kirschbaum, M.H.; Zain, J.; Prince, H.M.; Leonard, J.P.; Geskin, L.J.; et al. Phase II Multi-Institutional Trial of the Histone Deacetylase Inhibitor Romidepsin As Monotherapy for Patients with Cutaneous T-Cell Lymphoma. J. Clin. Oncol. 2009, 27, 5410–5417, doi:10.1200/jco.2008.21.6150.
  12. Kim, Y.H.; Bagot, M.; Pinter-Brown, L.; Rook, A.H.; Porcu, P.; Horwitz, S.M.; Whittaker, S.; Tokura, Y.; Vermeer, M.; Zinzani, P.L.; et al. Mogamulizumab versus vorinostat in previously treated cutaneous T-cell lymphoma (MAVORIC): An international, open-label, randomised, controlled phase 3 trial. Lancet Oncol. 2018, 19, 1192–1204. [
  13. 65. Piekarz, R.L.; Frye, R.; Turner, M.; Wright, J.J.; Allen, S.L.; Kirschbaum, M.H.; Zain, J.; Prince, H.M.; Leonard, J.P.; Geskin, L.J.; et al. Phase II Multi-Institutional Trial of the Histone Deacetylase Inhibitor Romidepsin As Monotherapy for Patients with Cutaneous T-Cell Lymphoma. J. Clin. Oncol. 2009, 27, 5410–5417, doi:10.1200/jco.2008.21.6150.
  14. 66. Child, F.; Ortiz-Romero, P.; Geskin, L.; Pérez-Ferriols, A.; Hellemans, P.; Elsayed, Y.; Phelps, C.; Forslund, A.; Kamida, M.; Zinzani, P.; et al. Phase II multicentre trial of oral quisinostat, a histone deacetylase inhibitor, in patients with previously treated stage IB-IVA mycosis fungoides/Sézary syndrome. Br. J. Dermatol. 2016, 175, 80–88, doi:10.1111/bjd.14427.
  15. 66. Child, F.; Ortiz-Romero, P.; Geskin, L.; Pérez-Ferriols, A.; Hellemans, P.; Elsayed, Y.; Phelps, C.; Forslund, A.; Kamida, M.; Zinzani, P.; et al. Phase II multicentre trial of oral quisinostat, a histone deacetylase inhibitor, in patients with previously treated stage IB-IVA mycosis fungoides/Sézary syndrome. Br. J. Dermatol. 2016, 175, 80–88, doi:10.1111/bjd.14427.
  16. Horwitz, S.M.; Kim, Y.H.; Foss, F.; Zain, J.M.; Myskowski, P.L.; Lechowicz, M.J.; Fisher, D.C.; Shustov, A.R.; Bartlett, N.L.; Delioukina, M.L.; et al. Identification of an active, well-tolerated dose of pralatrexate in patients with relapsed or refractory cutaneous T-cell lymphoma. Blood 2012, 119, 4115–4122, doi:10.1182/blood-2011-11-390211.
  17. Wang, E.S.; O’Connor, O.; She, Y.; Zelenetz, A.D.; Sirotnak, F.M.; Moore, M.A. Activity of a Novel Anti-folate (PDX, 10-propargyl 10-deazaaminopterin) against Human Lymphoma is Superior to Methotrexate and Correlates with Tumor RFC-1 Gene Expression. Leuk. Lymphoma 2003, 44, 1027–1035, doi:10.1080/1042819031000077124.
  18. Duvic, M.A.; Kim, Y.H.; Zinzani, P.L.; Horwitz, S.M. Results from a Phase I/II Open-Label, Dose-Finding Study of Pralatrex-ate and Oral Bexarotene in Patients with Relapsed/Refractory Cutaneous T-cell Lymphoma. Clin. Cancer Res. 2017, 23, 3552–3556, doi:10.1158/1078-0432.ccr-16-2064.
  19. 67. Horwitz, S.M.; Kim, Y.H.; Foss, F.; Zain, J.M.; Myskowski, P.L.; Lechowicz, M.J.; Fisher, D.C.; Shustov, A.R.; Bartlett, N.L.; Delioukina, M.L.; et al. Identification of an active, well-tolerated dose of pralatrexate in patients with relapsed or refractory cutaneous T-cell lymphoma. Blood 2012, 119, 4115–4122, doi:10.1182/blood-2011-11-390211.
  20. Wang, E.S.; O’Connor, O.; She, Y.; Zelenetz, A.D.; Sirotnak, F.M.; Moore, M.A. Activity of a Novel Anti-folate (PDX, 10-propargyl 10-deazaaminopterin) against Human Lymphoma is Superior to Methotrexate and Correlates with Tumor RFC-1 Gene Expression. Leuk. Lymphoma 2003, 44, 1027–1035.
  21. Horwitz, S.M.; Kim, Y.H.; Foss, F.; Zain, J.M.; Myskowski, P.L.; Lechowicz, M.J.; Fisher, D.C.; Shustov, A.R.; Bartlett, N.L.; Delioukina, M.L.; et al. Identification of an active, well-tolerated dose of pralatrexate in patients with relapsed or refractory cutaneous T-cell lymphoma. Blood 2012, 119, 4115–4122.
  22. Olek-Hrab, K.; Maj, J.; Chmielowska, E.; Jankowska-Konsur, A.; Olszewska, B.; Kręcisz, B.; Iwankowski, P.; Mackiewicz-Wysocka, M.; Adamski, Z.; Nowicki, R.; et al. Methotrexate in the treatment of mycosis fungoides—A multicenter observational study in 79 patients. Eur. Rev. Med. Pharmacol. Sci. 2018, 22, 3586–3594.
  23. Duvic, M.A.; Kim, Y.H.; Zinzani, P.L.; Horwitz, S.M. Results from a Phase I/II Open-Label, Dose-Finding Study of Pralatrexate and Oral Bexarotene in Patients with Relapsed/Refractory Cutaneous T-cell Lymphoma. Clin. Cancer Res. 2017, 23, 3552–3556.
  24. Olek-Hrab, K.; Maj, J.; Chmielowska, E.; Jankowska-Konsur, A.; Olszewska, B.; Kręcisz, B.; Iwankowski, P.; Mackiewicz-Wysocka, M.; Adamski, Z.; Nowicki, R.; et al. Methotrexate in the treatment of mycosis fungoides—A multicenter observational study in 79 patients. Eur. Rev. Med. Pharmacol. Sci. 2018, 22, 3586–3594.
  25. Duvic, M.A.; Kim, Y.H.; Zinzani, P.L.; Horwitz, S.M. Results from a Phase I/II Open-Label, Dose-Finding Study of Pralatrexate and Oral Bexarotene in Patients with Relapsed/Refractory Cutaneous T-cell Lymphoma. Clin. Cancer Res. 2017, 23, 3552–3556.
  26. Olek-Hrab, K.; Maj, J.; Chmielowska, E.; Jankowska-Konsur, A.; Olszewska, B.; Kręcisz, B.; Iwankowski, P.; Mackiewicz-Wysocka, M.; Adamski, Z.; Nowicki, R.; et al. Methotrexate in the treatment of mycosis fungoides—A multicen-ter observational study in 79 patients. Eur. Rev. Med. Pharmacol. Sci. 2018, 22, 3586–3594.
  27. Zackheim, H.S.; Kashani-Sabet, M.; McMillan, A. Low-dose methotrexate to treat mycosis fungoides: A retrospective study in 69 patients. J. Am. Acad. Dermatol. 2003, 49, 873–878, doi:10.1016/s0190-9622(03)01591-3.
  28. Zackheim, H.S.; Kashani-Sabet, M.; McMillan, A. Low-dose methotrexate to treat mycosis fungoides: A retrospective study in 69 patients. J. Am. Acad. Dermatol. 2003, 49, 873–878.
  29. Marchi, E.; Alinari, L.; Tani, M.; Stefoni, V.; Pimpinelli, N.; Berti, E.; Pagano, L.; Bernengo, M.G.; Zaja, F.; Rupoli, S.; et al. Gemcitabine as frontline treatment for cutaneous T-cell lymphoma: Phase II study of 32 patients. Cancer 2005, 104, 2437–2441.
  30. Duvic, M.; Talpur, R.; Wen, S.; Kurzrock, R.; David, C.L.; Apisarnthanarax, N. Phase II Evaluation of Gemcitabine Monotherapy for Cutaneous T-Cell Lymphoma. Clin. Lymphoma Myeloma 2006, 7, 51–58.
  31. Quereux, G.; Marques, S.; Nguyen, J.-M.; Bedane, C.; D’Incan, M.; Dereure, O.; Puzenat, E.; Claudy, A.; Martin, L.; Joly, P.; et al. Prospective Multicenter Study of Pegylated Liposomal Doxorubicin Treatment in Patients with Advanced or Refractory Mycosis Fungoides or Sézary Syndrome. Arch. Dermatol. 2008, 144, 727–733.
  32. Tirelli, U.; Errante, D.; van Glabbeke, M.; Teodorovic, I.; Kluin-Nelemans, J.C.; Thomas, J.; Bron, D.; Rosti, G.; Somers, R.; Zagonel, V.; et al. CHOP is the standard regimen in patients > or = 70 years of age with intermediate-grade and high-grade non-Hodgkin’s lymphoma: Results of a randomized study of the European Organization for Research and Treatment of Cancer Lymphoma Cooperative Study Group. J. Clin. Oncol. 1998, 16, 27–34.
  33. Shea, L.; Mehta-Shah, N. Brentuximab Vedotin in the Treatment of Peripheral T Cell Lymphoma and Cutaneous T Cell Lymphoma. Curr. Hematol. Malign Rep. 2020, 15, 9–19.
  34. Cho, A.; Jantschitsch, C.; Knobler, R. Extracorporeal Photopheresis—An Overview. Front. Med. 2018, 5, 236
  35. Edelson, R.; Berger, C.; Gasparro, F.; Jegasothy, B.; Heald, P.; Wintroub, B.; Vonderheid, E.; Knobler, R.; Wolff, K.; Plewig, G.; et al. Treatment of Cutaneous T-Cell Lymphoma by Extracorporeal Photochemotherapy. Preliminary results. N. Engl. J. Med. 1987, 316, 297–303
  36. Alfred, A.; Taylor, P.C.; Dignan, F.; El-Ghariani, K.; Griffin, J.; Gennery, A.R.; Bonney, D.; Das-Gupta, E.; Lawson, S.; Malladi, R.K.; et al. The role of extracorporeal photopheresis in the management of cutaneous T-cell lymphoma, graft-versus-host disease and organ transplant rejection: A consensus statement update from the UK Photopheresis Society. Br. J. Haematol. 2017, 177, 287–310.
More
This entry is offline, you can click here to edit this entry!
ScholarVision Creations