Response to Chlormethine/Mechlorethamine gel Maintenance Treatment Regimen in Patients With Mycosis Fungoides: A Single-center Retrospective Study.

BACKGROUND: Mycosis fungoides (MF), the most common subtype of Cutaneous T-cell lymphomas, is caused by malignant T-cell proliferations in the skin that can invade blood, lymph nodes, or viscera. Currently, data on efficacy of maintenance therapies in MF are lacking. We developed a unique protocol to use chlormethine/mechlorethamine 0.016% gel formulation as maintenance regimen for MF patients in remission. PURPOSE: To determine progression-free survival and efficacy of chlormethine/mechlorethamine as maintenance and active treatment regimens for MF. MATERIALS AND METHODS: A retrospective review of MF patients seen at Thomas Jefferson University from 2012 to 2020 was conducted. Patients of all stages treated with chlormethine/mechlorethamine as maintenance or active treatment with 2 consecutive mSWATs (modified Severity Weighted Assessment Tool) documented were included. Treatment outcomes were assessed by change in mSWAT and progression-free survival. Dermatology Life Quality Index surveys before and after treatment were analyzed. RESULTS: Of 186 MF patients, 44 met inclusion criteria. Patients on maintenance therapy had a 65.22% progression-free survival rate with median time to progression of 29.45 months. By-time analysis for responders on active and maintenance treatment showed an increased response over time. Peak responses were seen at last mSWAT recorded. Both cohorts experienced improved quality-of-life scores from initiation to discontinuation of chlormethine/mechlorethamine. CONCLUSION: Patients on maintenance and active chlormethine/mechlorethamine treatment regimens demonstrated improvement in mSWAT and quality-of-life. Chlormethine/mechlorethamine treatment showed progression-free survival for a median of 29.45 months, indicating this therapy may be an effective maintenance regimen.

Lung cancer and other second neoplasms after treatment of Hodgkin lymphoma.

PURPOSE: To evaluate the risk factors associated with lung cancer (LC) and other second neoplasms (SN) in Hodgkin lymphoma (HL) survivors. METHODS: We retrospectively analyzed the clinical characteristics and outcomes of 604 patients treated in our institution between 1968 and 2012. RESULTS: 90 out of 604 patients developed SN: 27 LC and 63 other SN. The median time elapsed until LC and other SN was 16.5 and 11.8 years, respectively (p = 0.003). In the LC group, 85.5 % of patients were male and 84.6 % smokers (HR 7, 95 % CI 2.4-20.7, p < 0.001). Radiotherapy (RT) doses applied were higher in the SN group with an increased risk of LC (HR: 4.0 95 % CI 1.1-11.6, p = 0.010) and other SN (HR: 3.3 95 % CI 1.6-6.7 p = 0.001) with doses higher than 42 Gy. No association was found between alkylating agents and development of SN. In LC, the most frequent histology was adenocarcinoma with an elapsed time after HL of 13.2 years in early stages and 21.3 in advanced (p = 0.02). Median OS after a diagnosis of LC was 12.6 months ranging from 5.9 (in cases presenting due to symptoms) to 49.1 (incidentally diagnosed cases) (p = 0.005). CONCLUSIONS: RT treatment, especially with doses higher than 42 Gy, and smoking increase the risk of SN after HL. In this series, LC patients with early stages had a shorter elapsed time from HL diagnosis and longer OS, therefore the role of LC screening in HL survivors should be prospectively evaluated and smoking cessation counseling ought to be a key aspect during follow-up.

Tratamiento de la alopecia areata / Treatment of the alopecia areata

En una patología como la alopecía areata, la que se presenta de distintas formas clínicas, con asociaciones variadas, donde las remiciones son posibles y los tratamientos disponibles no son 100 por ciento eficaces, es dificil evaluar la terapéutica más adecuada. lLos tratamientos disponibles pueden dividirse en tópicos y sistémicos. Los corticoides ocupan un lugar importante en el arsenal terapéutico, en especial los tópicos o en inyecciones intralesionales. Otrs productos se usan con resultados varioables como la inminoterapia tópica, en especial con el minoxidil, la difenciprona y la antralina. La medicación sistïrmica se reserva para casos severos (corticosteroides,ciclosporina A, etc). La mayoría actuarían alterando la respuesta inmune y en otros en controvertida. Consideramos a la afección dentro de su marco general, más que etético, pero sin descuidar la integridad del individuo y hacia esto debemos apuntar en nuestra estrategia de tratamiento. La relación paciente-médico es fundamental para manejar esta enfermedad en la que aún no tenemos una medicación curativa.

Tratamiento de la alopecia areata / Treatment of the alopecia areata

En una patología como la alopecía areata, la que se presenta de distintas formas clínicas, con asociaciones variadas, donde las remiciones son posibles y los tratamientos disponibles no son 100 por ciento eficaces, es dificil evaluar la terapéutica más adecuada. lLos tratamientos disponibles pueden dividirse en tópicos y sistémicos. Los corticoides ocupan un lugar importante en el arsenal terapéutico, en especial los tópicos o en inyecciones intralesionales. Otrs productos se usan con resultados varioables como la inminoterapia tópica, en especial con el minoxidil, la difenciprona y la antralina. La medicación sist´rmica se reserva para casos severos (corticosteroides,ciclosporina A, etc). La mayoría actuarían alterando la respuesta inmune y en otros en controvertida. Consideramos a la afección dentro de su marco general, más que etético, pero sin descuidar la integridad del individuo y hacia esto debemos apuntar en nuestra estrategia de tratamiento. La relación paciente-médico es fundamental para manejar esta enfermedad en la que aún no tenemos una medicación curativa. (AU)

[Multiple neoplasms after a well succeeded treatment of Hodgkin's disease]. / Neoplasias múltiplas após tratamento bem sucedido de doença de Hodgkin.

The authors refer to a 21-year-old Caucasian (white) woman, who in 1977 presented fever and cervical and axillary adenopathy, whose biopsy showed nodular sclerosis Hodgkin's Disease, stage IIIB. The patient received six chemotherapy cycles associated with immunotherapy and supplemented with radiation therapy with good response. RESULTS--In 1985, after routine gynaecological examination and a hysterectomy, cervical intraepithelial neoplasia grade 3 (CIN 3) and atypic leiomyoma of the uterine body were diagnosed. Five years later, biopsies diagnosed invasive duct carcinoma in the right breast and homolateral axillary and cervical nodes. The patient was submitted to chemo and radiation therapy and died nine months later. CONCLUSION--The possibility of later occurrence of a second or multiple new malignancies in patients successfully treated for Hodgkin's Disease points out the need for a more complete long-term follow-up, including periodic mammography.

[Non-Hodgkin's lymphoma secondary to Hodgkin's disease treated with chemo- and radiotherapy. Report of a case]. / Linfoma no Hodgkin secundario a enfermedad de Hodgkin tratada con quimio- y radioterapias. Informe de un caso.

In 18 years of experience in the use of combined chemotherapy in Hodgkin's disease at the Instituto Nacional de la Nutrición Salvador Zubirán, the first case of non-Hodgkin's lymphoma secondary to Hodgkin's disease was identified. The patient was a 23 year old male who initially developed a nodular sclerosis type of Hodgkin's disease. Three years later, the biopsies showed lymphocyte predominance type of Hodgkin's disease. Finally, one year later, the patient developed a diffuse small cleaved cell lymphoma. Non-Hodgkin's lymphoma occurring in patients treated with combined chemotherapy and radiotherapy after Hodgkin's disease is a rare complication. We believe that the genesis of a second neoplasm in these cases may be due to both disturbances in the cellular immunity intrinsic to Hodgkin's disease and the treatment with combined chemotherapy and radiotherapy.

Hodgkin's disease and acute leukemia. Is it a true association?

The incidence of secondary malignancy was assessed in 537 patients with Hodgkin's disease treated with radiotherapy (128 patients), chemotherapy alone (156 patients), or in combined modality therapy (253 patients) between January 1973 to September 1985 with a median follow-up of 7.5 years. The dose of radiation therapy, dose of cytotoxic drugs and sequence of treatment was carefully analyzed. No cases of acute leukemia or other secondary malignant disease were identified in these cases. No differences in clinical laboratory features or treatments were identified in relation to previous reports. Racial difference is the unique feature which seems to avoid the development of this complication in patients treated for Hodgkin's disease. We hope that other reports in Latin America can contribute to the identification of race as the difference.

[Hodgkin's disease during pregnancy. Study of late effects in the newborn infants]. / Enfermedad de Hodgkin durante el embarazo. Estudio de efectos tardíos en los recién nacidos.

An analysis of the possible late effects in 15 children of mothers with Hodgkin Disease, who were given combined chemotherapy during pregnancy, including five who were in the first trimester of development, was conducted. None of the newborns were found to have congenital abnormalities during birth. The 15 children, ranging in ages between 4 to 17, are alive, showing both normal physical and psychomotor development, as well as normal laboratory and cytogenetic results. The thirteen mothers who were in complete remission as a result of the chemotherapy used at recommended dosages and at accepted intervals, are alive and without any evidence of the illness, considering them as cured. Based on these results, pregnancy should not be considered as a contraindication for the adequate treatment of Hodgkin's disease, since those fetuses who received cytotoxic agents in utero, did not show a greater incidence of congenital malformations and have not shown any evidence of side-effects due to the chemotherapy.

Topical nitrogen mustard: an effective treatment for cutaneous Langerhans cell histiocytosis.

In 16 children with multisystem Langerhans cell histiocytosis (mean age 22 months, range 5 to 36 months) severe symptomatic skin involvement was treated with topical nitrogen mustard (mechlorethamine hydrochloride). In each case, rapid clinical improvement occurred within 10 days; subsequent complete healing was observed in 14 children, and partial healing in 2 others in whom treatment was a component of palliative care. Mean duration of treatment was 3.5 months (range 2 to 6 months). Systemic treatment was averted in 11 patients because response to topical therapy was so favorable, but bone marrow or respiratory failure led to a fatal outcome in 5 other patients. Adverse effects were minimal. One patient developed contact allergy to topical nitrogen mustard after 2 years of intermittent therapy, but was successfully desensitized and was then able to continue treatment. We conclude that the topical application of nitrogen mustard is an effective treatment for cutaneous Langerhans cell histiocytosis. Although adverse effects were minimal in the short term, there remains concern about the possibility of long-term cutaneous carcinogenicity.

Randomized study for the treatment of advanced Hodgkin's disease: MOPP vs. LOPP.

Between January 1983 and December 1984, 83 patients with advanced Hodgkin's disease were entered in a prospective randomized trial comparing MOPP (mechlorethamine, vincristine, procarbazine and prednisone) with a regimen containing chlorambucil (Leukeran), vincristine, prednisone and procarbazine (LOPP). Both groups were comparable for the variables of age, stage, symptoms, histology and sites of involvement. Seventy percent of LOPP-treated patients achieved a complete remission compared to 65% of the MOPP-treated group. After a median follow-up of greater than 48 months, there is no statistical difference between the two treatment groups in survival or relapse free-survival. The LOPP combination was better tolerated with significantly less side effects. The drug regimen LOPP appears to be as effective as MOPP in producing complete remission and long term survival in patients with advanced Hodgkin's disease.

Hodgkin's disease. A historical perspective.

Two hundred and sixty-four patients with Hodgkin's disease (HD) forming the basis of our 15 year experience are retrospectively analyzed. Three therapeutic periods are recognizable. 1. The 1974-76 period was characterized by the increasing knowledge of staging procedures and therapeutic approaches. The 81 patients treated in this period experience 67 and 60% survival at 5 and 10 years, respectively. 2. The 1977-80 period was characterized by a large combination of MOPP and radiotherapy. The 87 patients who entered this period experienced 75 and 72% survival at 5 and 10 years, respectively. 3. The last therapeutic period 1981-84 is characterized by the increasing relevance of prognostic factors and alternating the use of MOPP and ABVD as non-cross resistant regimen. The 96 patients who entered this period showed 96% survival at 4 years. Both survival and disease-free survival were positively influenced by the change of therapeutic strategies during the three periods (p less than .005). Although better results have been recorded moving from one to the next therapeutic period, the present policy has been also based on the recognition of a high number of late complications due to therapy. Preliminary results about the present therapeutic experience seem to indicate both a good remission rate and low incidence of complications.

[Acute myeloid leukemia after treatment of Hodgkin's disease]. / Leucemia mielóide aguda após tratamento da doença de Hodgkin.

The development of acute leukemia, particularly acute myeloid leukemia, represents a serious complication in patients treated with radio and/or chemotherapy for Hodgkin's disease. It has been reported with increasing frequency in the last years. Two such cases, that occurred in 87 patients treated for Hodgkin's disease, are reported. Complete autopsy was performed in both. The patients were less than 30 years old, received combined therapy during a prolonged time (more than 12 months), with an interval superior to 44 months between the diagnosis of Hodgkin's disease and the appearance of acute myeloid leukemia. The survival time was less than 12 months. Residual Hodgkin's disease was not observed.

Long-term efficacy, curative potential, and carcinogenicity of topical mechlorethamine chemotherapy in cutaneous T cell lymphoma.

Complete responses lasting from 4 to 14 years were documented in 65 of 331 (20%) patients with cutaneous T cell lymphoma treated with topical mechlorethamine (HN2) between 1968 and 1982. Such long-lasting remissions occurred most often, but not invariably, in patients with patch or plaque phase mycosis fungoides without palpable lymphadenopathy (stage Ia or Ib). The likelihood of a continuous remission was enhanced by initiation of treatment before an unequivocal pathologic diagnosis. Despite the long-lasting responses in these patients, however, relapses have been documented in 11 (17%) of these patients, and all relapses occurred within 8 years of discontinuing maintenance topical chemotherapy. Thus, in our experience, a continuous remission lasting 8 or more years provides evidence that cutaneous T cell lymphoma can be eradicated by aggressive topical chemotherapy. This circumstance was observed in 35 patients, representing a cure rate of at least 11% overall. In addition, when compared with the general population of the United States, patients who received topical HN2 were at an 8.6-fold and a 1.8-fold increased risk for the development of squamous cell carcinoma and enhanced for Hodgkin's disease and colon cancer but not for systemic cancers known to be induced by systemic administration of alkylating drugs. These results compare favorably with experiences with topical HN2 chemotherapy at other centers but raise questions about the risks associated with long-term administration for maintenance of remissions.