Long-term remission after allogeneic hematopoietic stem cell transplantation for refractory cutaneous T-cell lymphoma

BACKGROUND: Allogeneic hematopoietic stem cell transplantation has proved to be an effective therapeutic option in various hematologic neoplastic disorders. Because patients with advanced cutaneous T-cell lymphoma have a poor prognosis, with minimal possibilities of sustained remission, we studied the therapeutic potential of hematopoietic stem cell transplantation. OBSERVATIONS: Three young patients with refractory tumor stage mycosis fungoides underwent allogeneic HLA-matched sibling transplantation with combined marrow and CD34-enriched peripheral blood stem cell transplantation after cytoreductive chemotherapy and total-body irradiation. Complete and sustained clinical and histologic remission was achieved in 2 patients, and both remain disease free 4(1/2) years and 15 months later. One patient was in complete remission for 9 months, followed by limited cutaneous recurrence. Mild graft-vs-host disease and graft-vs-tumor effect have contained the recurring disease as a low-grade process. CONCLUSIONS: Allogeneic hematopoietic stem cell transplantation has the potential for sustained remission and the possibility of cure for young patients with advanced and recalcitrant cutaneous T-cell lymphoma. Even in the absence of complete remission, an allogeneic graft-vs-tumor effect may provide an immune mechanism to control the malignant T-cell process and alter the natural history of disease.     

Hematopoietic stem cell transplantation in advanced cutaneous T‐cell lymphoma

We retrospectively reviewed data pertaining to five patients with cutaneous T‐cell lymphoma (CTCL) who had received hematopoietic stem cell transplantation (HSCT) between 2004 and 2015 at Kurume University Hospital, along with their clinical data until March 2016. For patients with advanced CTCL eligible for HSCT, autologous HSCT was performed when they responded well to chemotherapy, and allogeneic HSCT was selected for patients with advanced mycosis fungoides (MF)/Sézary syndrome (SS) and CTCL other than MF/SS with poor chemosensitivity. Two patients (primary cutaneous anaplastic large cell lymphoma and primary cutaneous CD8⁺ aggressive epidermotropic cytotoxic T‐cell lymphoma) who responded well to chemotherapy received autologous HSCT: one patient was alive in partial remission and the other died due to therapy‐related acute myeloid leukemia without disease relapse. In the remaining three patients with MF or SS, allogeneic HSCT was performed. Although one patient with MF died due to disease progression, the remaining two patients were alive in complete remission. Although there were two deaths in this study, the outcomes were considered satisfactory.     

Autologous hematopoietic stem cell transplantation followed by oral bexarotene in a patient with advanced mycosis fungoides

We describe the case of a 17-year-old patient with rapidly progressing and aggressive mycosis fungoides, with multiple cutaneous tumors and large cell transformation. She was initially treated with 3 cycles of high-dose chemotherapy with mega-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) without response, leading to the decision to undertake autologous hematopoietic stem cell transplantation. Partial remission of the disease was achieved with this treatment and subsequent introduction of oral bexarotene led to complete remission, which has been maintained for more than 3 years with good tolerance of oral therapy. We discuss the advantages and disadvantages of autologous hematopoietic stem cell transplantation and the use of oral bexarotene.     

Hematopoietic stem cell transplantation for cutaneous T‐cell lymphoma: Summary of 11 cases from two facilities in Japan and Brazil

Some patients with cutaneous T‐cell lymphoma (CTCL) show a miserable clinical course and the only option that can induce long‐term remission for advanced CTCL may be hematopoietic stem cell transplantation (HSCT). So far, studies on HSCT for CTCL patients have been limited. In this study, we summarized 11 cases with CTCL treated with HSCT, including nine cases in Japan and two cases in Brazil. The patients were five cases with mycosis fungoides (MF), two cases with Sézary syndrome (SS), three cases with anaplastic large cell lymphoma, and one case with primary cutaneous peripheral T‐cell lymphoma, not otherwise specified (PTL‐NOS). Currently, seven out of 11 cases are alive (at 13–108 months after transplantation) and four died at 15 days to 14 months after transplantation. When focusing on the eight patients who received allogeneic HSCT for MF/SS and PTL‐NOS, all four patients at 45 years old or under are alive at present. One case showed relapse in the skin. On the other hand, one out of the other four patients at over 45 years old survived. Engraftment failure was seen in one case and all the other three cases experienced relapse. Although this is only a case series with a small number, our study has suggested that we should be careful about age when treating patients with MF/SS by allogeneic HSCT.     

ALK‐positive primary cutaneous T‐cell‐lymphoma (CTCL) with unusual clinical presentation and aggressive course

Anaplastic lymphoma kinase (ALK) expression is uncommon in primary cutaneous T‐cell‐lymphomas (CTCL). We report the case of a patient who was initially diagnosed with small plaque parapsoriasis, and eventually developed an unusual manifestation of CTCL 6 years later. The disease was characterized by aggressively ulcerating plaques and tumors of the entire skin. Histopathology revealed monoclonal proliferation of atypical T‐lymphocytes and CD30‐positive blasts with expression of ALK and identification of an ATIC‐ALK fusion protein. Extensive staging confirmed the primary cutaneous origin of the lymphoma. After failure of several conventional treatments including polychemotherapy, the patient finally achieved remission after receiving brentuximab‐vedotin, alemtuzumab and subsequent allogeneic stem cell transplantation. In the following, the patient developed inflammatory cutaneous lesions that pathologically showed no evidence for lymphoma relapse or classical cutaneous graft‐versus‐host disease. The patient responded to immunosuppression, but finally died from multi‐organ failure due to sepsis 8 months after stem cell transplantation. This is a rare instance of ALK positivity in a CTCL, most likely resembling CD30+ transformed mycosis fungoides, because it was not typical for cutaneous anaplastic large cell lymphoma (ALCL). In contrast to its role in systemic ALCL as favorable prognostic marker, ALK expression here was associated with an aggressive course.     

Mycosis fungoides stage IB progressing to cutaneous tumors

A 44-year-old African American woman presented with well-demarcated, pruritic and intermittently painful plaques and subsequently a diagnosis of mycosis fungoides stage IB was made. Six months after diagnosis, cutaneous tumors developed despite treatment with narrow-band ultraviolet B phototherapy. The patient failed low-dose methotrexate treatment and is now slowly improving on combination therapy with subcutaneous interferon alfa and oral bexarotene. This patient demonstrates the progression of patch/plaque stage disease to cutaneous tumors. Her case highlights the use of interferon and combination therapies in more advanced mycosis fungoides and demonstrates potential difficulties encountered in treating skin of color.     

Association of mycosis fungoides and Hodgkin's disease

A 69-year-old man developed a Hodgkin's disease 2 years after he started a mycosis fungoides. He presented cutaneous plaques of mycosis fungoides. The first signs of Hodgkin's disease was acquired ichthyosis and loss of weight. Echotomography of the abdomen showed retroperitoneal nodes. A laparotomy was performed and the histopathologic examination of the lymph nodes revealed a Hodgkin's disease type 2 (sclero-nodular). The liver and the bone marrow were involved. A chemotherapy was completed but the patient died 10 months later. The review of the literature showed 24 patients with Hodgkin's disease and mycosis fungoides or Sézary syndrome. Relation between mycosis fungoides, Hodgkin's disease and lymphomatoid papulosis are discussed.     

蕈样肉芽肿误诊为蛎壳状银屑病1例

报告1例被误诊为蛎壳状银屑病的蕈样肉芽肿。患者男，48岁。因全身皮疹32年，加重2个月就诊。32年前发现双侧股部片状红斑脱屑，病情逐渐发展，2个月前全身出现蛎壳状皮疹，1个月前左侧腰部及股部出现肿物，在外院诊断为“蛎壳状银屑病”。因经治不愈转至我科。结合临床及病理检查确诊为蕈样肉芽肿(肿瘤期)。半年后患者死于脑、肺、肝、骨转移。     

Induction of complete remission of advanced stage mycosis fungoides by allogeneic hematopoietic stem cell transplantation

Advanced mycosis fungoides (MF) is incurable with conventional treatments. High-dose chemoradiotherapy with autologous bone marrow transplantation has induced remissions in a small number of patients with MF, but this modality is limited by a high relapse rate. We report induction of complete remission in a 37-year-old woman with rapidly progressive stage IV MF with allogeneic stem cell transplantation (Allo SCT). She remains in continuous complete remission 2 years after transplant. Allo SCT for MF is theoretically attractive, because there is no contamination of the graft by malignant cells, and because of the possibility of graft-versus-tumor effect. Although the results in this patient are encouraging, more patients and longer follow-up are needed to define the usefulness of Allo SCT in the treatment of MF.     

Mycosis fungoides with involvement of the oral cavity

Mycosis fungoides rarely involves the oral cavity. To our knowledge only 29 cases of oral cutaneous T-cell lymphoma have been described up to 1994. This report presents a case of mycosis fungoides with involvement of the oral cavity in a 57-year-old man who died from septicemia 7 months after the onset of oral involvement.     

Uncommon presentation of mycosis fungoides: eyelid margin involvement

Mycosis fungoides is a cutaneous T-cell lymphoma that has been rarely reported to involve ocular structures. A 33-year-old woman who had received therapy for mycosis fungoides on the trunk for 11 years, presented to our clinic with new plaques and tumors on her eyebrows and eyelid margin, and alopecia of her eyelashes and eyebrow. The histopathological examinations supported the diagnosis of mycosis fungoides. There was no intraocular involvement with tumor. The mycosis fungoides was of stage II B, and the patient was referred to medical oncology and radiation oncology clinics for treatment. She was placed on a radiotherapy schedule. The involvement of mycosis fungoides in the ocular area is rare in the published work. The importance of eye involvement is being seen in advanced cases, and there is a possible association between mycosis fungoides and poor prognosis by being an indicator of systemic involvement.     

Erfolgreicher Einsatz einer allogenen Stammzelltransplantation bei therapierefraktärer Mycosis fungoides

Mycosis fungoides is the most common type of cutaneous T-cell lymphoma and characterized by a chronic progressive course spanning decades. The choice of treatment options should be tailored to the stage depending on the extent and aggressiveness of the disease and taking the individual situation of the patient into consideration. Long-term complete remissions can only be achieved in the early phase of the disease, while there is no therapy that results in a cure or long-term remission in advanced stages. In young patients with a treatment-refractory course of mycosis fungoides, allogeneic stem cell transplantation represents an important alternative option to manage the disease since complete clinical remission can be obtained even in advanced stages.     

Total cutaneous electron beam therapy of mycosis fungoides

Electron beam irradiation of the entire skin surface was used to treat 25 patients with mycosis fungoides from 1977 to January 1988. A plexiglas screen was used to reduce the energy of the 8 MeV beam of a Sagittaire linear accelerator to 4 MeV. A total dose of 30 Gy was delivered in 12 fractions over days. This series includes 17 men and 8 women with a mean age of 44 years (range 13-78 years) and a mean follow-up of 34 months (range 6-92 months). The following-up staging system was used: stage A: superficial lesions covering less than 50 p. 100 of the body surface; stage B: superficial lesions covering more than 50 p. 100 of the body surface; stage C: tumors of the skin, lymph nodes and/or visceral organs, Sezary's syndrome. All stage A patients achieved complete remission. One developed recurrent disease in a very limited area 17 months after radiation therapy. No stage A patient died of mycosis fungoides. 6/9 stage B patients achieved complete remission; 4 of these developed recurrent disease localized to the skin 6 to 13 months after electron therapy. These recurrences were controlled by topical nitrogen mustard, puva therapy or localized irradiation. 1 patient showed no response and died of cutaneous mycosis fungoides. 5/10 stage C patients obtained complete remission but all relapsed within a mean period of 7 months. 4/5 of the patients not responding to electron therapy died of their disease and one is alive 16 months after completion of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Long-term remission of stage IVa mycosis fungoides following treatment with I-131 for concomitant thyroid carcinoma

Background Treatment in advanced stage mycosis fungoides is often palliative. New approaches, like radioimmunotherapy, are necessary. However, only partial responses or short-term remissions are ohtained with all these methods.
Case report: A 37-year-old female had a tumor stage mycosis fungoides and a thyroid carcinoma with lymph node involvement. Both tumors are now in complete remission 9 years after following a combined treatment with I-131 (total dose 250 mCi).
Conclusion: Further studies are needed to assess the role of I-131 in the treatment of mycosis fungoides.     

Mycosis fungoides with focal CD 30 transformation in an adolescent

Mycosis fungoides is rare in children and adolescents. Large cell transformation in mycosis fungoides is typically seen in adult patients with advanced disease. We describe a 16-year-old girl with patch/plaque stage mycosis fungoides who developed a nodule within one of the plaques, which on histopathology showed large cell transformation, with positive labeling with the CD30 immunostain. To the best of our knowledge, this is the second reported case of mycosis fungoides with CD30+ large cell transformation in a child.     

[开放获取] 蕈样肉芽肿治疗中国专家共识（2023）

【摘要】 蕈样肉芽肿（MF）是皮肤T细胞淋巴瘤最常见类型,早期仅累及皮肤,进展期出现肿块并有淋巴结、外周血和内脏受累。治疗前需对患者进行分期评估,根据分期选择治疗方案。我国12位MF诊疗领域专家在国外最新指南和共识的基础上,回顾了治疗方法的循证医学级别,结合我国现状,在MF一线、二线治疗方案和新疗法等方面达成共识,为规范MF治疗提供指导。     

Mycosis fungoides und Sézary-Syndrom – Überblick und Ausblick

Mycosis fungoides and Sézary syndrome are the most important representatives of the heterogeneous group of cutaneous T-cell lymphomas. The diseases are rare and the diagnosis, which always requires a clinical-pathological correlation, is often delayed, especially in early forms of mycosis fungoides. The prognosis of mycosis fungoides depends on its stage and is usually favorable in the early stages. Clinically relevant prognostic parameters are missing and their development is the subject of current clinical research. Sézary syndrome, characterized by initial erythroderma and blood involvement, is a disease with a high mortality rate, in which good responses can now be achieved in many cases with new treatment options. The pathogenesis and immunology of the diseases is heterogeneous, with recent results pointing primarily to changes in specific signal transduction pathways that may be suitable as future treatment targets. Current therapy for mycosis fungoides and Sézary syndrome is primarily palliative with topical and systemic options either used alone or in combination. Only with allogeneic stem cell transplantation durable remissions can be achieved in selected patients. Similar to other areas of oncology, the development of new therapies for cutaneous lymphomas is currently changing from relatively untargeted empiricism to disease-specific, targeted pharmacotherapy based on knowledge from experimental research.     

Analysis of T-cell antigen receptor gamma chain gene rearrangement by polymerase chain reaction in combination with denaturing gradient gel electrophoresis in the differential diagnosis of cutaneous T-lymphoproliferative diseases

A polymerase chain reaction (PCR)-based strategy has been developed for analysis of clonal rearrangement of the T-cell receptor gamma gene (TCR gamma) and was shown to be useful for detection of clonal T-cell populations. In this study, we performed PCR combined with denaturing gradient gel electrophoresis (DGGE) on fresh frozen biopsy samples from 16 patients with cutaneous T-lymphoproliferative diseases in whom a definite diagnosis was difficult to make on morphological and immunohistochemical grounds alone. Ages of the patients at biopsy ranged from 28 to 81 (median 62) years, and the subjects consisted of 8 men and 8 women. They presented with erythema on the extremities in 5 cases, trunk in 7, buttock in 2, and papules on the trunk and face in one case each. Clonal rearrangement of TCR gamma was observed in 3 of 16 cases. Clinical diagnoses of these three cases were mycosis fungoides, cutaneous invasion of adult T-cell leukemia (ATL), and large granular lymphocytic leukemia (LGL) of T-cell type, respectively, but they were histologically difficult to differentiate from reactive cutaneous T-cell proliferation. The skin lesions of the LGL case worsened, and this patient died two years after biopsy. Another patient with suspected mycosis fungoides in the plaque stage died due to dissemination of tumors 22 months after biopsy. The remaining one patient with ATL survived with cutaneous lesions for over four years. Clonality was not demonstrated in the remaining 13 cases, and their clinical courses were favorable. These findings showed that demonstration of clonal TCR gamma gene rearrangement using the PCR-DGGE method is very helpful for diagnosis of cutaneous T-cell neoplasms.     

Follicular Mucinosis in a Male Adolescent with a History of Acute Myelogenous Leukemia and Graft‐versus‐Host Disease

Although many cases of follicular mucinosis are idiopathic, numerous others are associated with mycosis fungoides or, rarely, other neoplastic or inflammatory disorders. There are only three reported cases, all in adults, of follicular mucinosis arising in association with acute myelogenous leukemia, two of which involved mycosis fungoides–associated follicular mucinosis, including one case in which the patient had a preceding bone marrow transplant. We present the first reported case of follicular mucinosis arising in an adolescent with acute myelogenous leukemia and acute graft‐versus‐host disease after an allogeneic bone marrow transplantation.     

Alemtuzumab in Sézary syndrome: efficient but not innocent

Mycosis fungoides is the most common form of cutaneous T-cell lymphomas. The related Sézary syndrome is a more aggressive form in which the skin is diffusely affected and the peripheral blood is involved. Although easily managed during its early phases, late-stage mycosis fungoides/Sézary syndrome is usually difficult to treat and becomes refractory to chemotherapy. Recently, promising case-based results have been obtained with alemtuzumab, a humanized immunoglobulin G1 monoclonal antibody that binds to CD52 cell surface antigens, in the treatment of advanced stage mycosis fungoides/Sézary syndrome. We report a case of Sézary syndrome treated successfully with alemtuzumab but who died of treatment-related infection.