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Permanent chemotherapy-induced alopecia: A review

      To the Editor: Hair loss in patients undergoing chemotherapy for cancer is usually reversible after discontinuation of chemotherapy. However, in chemotherapy-induced permanent alopecia (CIPAL) characterized by absent or sparse hair, regrowth may not occur.
      • Park J.Y.
      • Choi Y.S.
      • Lee W.J.
      • Lee S.J.
      • Na G.Y.
      • Kim D.W.
      • et al.
      Five cases of permanent alopecia following chemotherapy.
      • Machado M.
      • Moreb J.S.
      • Khan S.A.
      Six cases of permanent alopecia after various conditioning regimens commonly used in hematopoietic stem cell transplantation.
      • Prevezas C.
      • Matard B.
      • Pinquier L.
      • Reygagne P.
      Irreversible and severe alopecia following docetaxel or paclitaxel cytotoxic therapy for breast cancer.
      • Puglisi F.
      • Aprile G.
      • Sobrero A.
      Tamoxifen-induced total alopecia.
      • Tornebohm-Roche E.
      • Merup M.
      • Lockner D.
      • Paul C.
      Alpha-2a interferon therapy and antibody formation in patients with essential thrombocythemia and polycythemia vera with thrombocytosis.
      After institutional review board approval, we performed a retrospective chart study of patients who had attended our Hair Clinic during the previous 7 years. Findings were compared with reports identified by a literature search.
      We reviewed 8,430 records of patients with nonscarring alopecia. Of these, 7 cases of CIPAL were identified (0.083%), two following chemotherapy with busulphan and 5 following treatment with taxanes (Table I). The median age of these patients was 41 years and all showed diffuse alopecia characterized by short and sparse scalp hair (Fig 1), which developed a few weeks after the start of chemotherapy. Two patients also demonstrated partial eyebrow loss. Histopathologic examination showed a marked reduction of follicular units with an increase in vellus hair formation and absence of any significant inflammation or scarring.
      Table IDetails of studies that report chemotherapy-induced permanent alopecia (CIPAL)
      Study, yearNo. of patientsSex (male:female)Age (y) (median, range)DiseaseClinical subtypes of CIPALChemotherapy agents
      Current study, 200970:741 (22-68)Breast cancer, germ cell cancersDiffuse w/or w/o loss of eyebrowsDoCi, DoEp, DoEpCy, BuCy, BuMel
      Prevezas et al
      • Prevezas C.
      • Matard B.
      • Pinquier L.
      • Reygagne P.
      Irreversible and severe alopecia following docetaxel or paclitaxel cytotoxic therapy for breast cancer.
      20:256.5 (55-58)Breast cancerDiffuse (scalp and body); androgenetic type (50%)DoLe, Pa
      Machado et al
      • Machado M.
      • Moreb J.S.
      • Khan S.A.
      Six cases of permanent alopecia after various conditioning regimens commonly used in hematopoietic stem cell transplantation.
      62:445 (37-65)Germ cell cancers, Ewing’s sarcomaComplete (50%) w/or w/o facial hair loss; incomplete (33%); patchy (17%)BuCy, BuCyVP16, CyTBI, CyVP16TBI
      Park et al
      • Park J.Y.
      • Choi Y.S.
      • Lee W.J.
      • Lee S.J.
      • Na G.Y.
      • Kim D.W.
      • et al.
      Five cases of permanent alopecia following chemotherapy.
      51.420 (18-43)Germ cell cancers, malignant rhabdoid tumor, Ewing’s sarcomaDiffuseBuCy, CyViAc, Bu, CyViAdVP16
      de Jonge et al
      Data from Machado et al.2
      , 2002
      17NR43 (16-59)Breast cancer, germ cell cancers, ovarian cancerComplete (47%); incomplete (53%)CTC
      Puglisi et al,
      • Puglisi F.
      • Aprile G.
      • Sobrero A.
      Tamoxifen-induced total alopecia.
      2001
      1Female53Breast cancerCompleteTamoxifen
      Tran et al
      Data from Machado et al.2
      , 2000
      1Female23Germ cell cancersComplete (scalp, axilla, pubic region)BuCy
      Ayoub et al
      Data from Puglisi et al.4
      , 1997
      1FemaleNRBreast cancerDiffuseTamoxifen
      Gateley et al
      Data from Puglisi et al.4
      , 1997
      1Female62Breast cancerAndrogenetic typeTamoxifen
      Liungman et al
      Data from Machado et al.2
      , 1995
      3116:1536 (7-16)Germ cell cancers, enzyme defect, aplastic anemiaComplete or incomplete (61%), NR (39%)BuCy
      Tornebohm-Roche et al,
      • Tornebohm-Roche E.
      • Merup M.
      • Lockner D.
      • Paul C.
      Alpha-2a interferon therapy and antibody formation in patients with essential thrombocythemia and polycythemia vera with thrombocytosis.
      1995
      1FemaleNREssential thrombocytopeniaCompleteInterferon alfa-2a
      Vowels et al
      Data from Machado et al.2
      , 1993
      189:96.8 (6 mo-20 y, 3 mo)Germ cell cancers, neuroblastoma, malignant histiocytosis, storage disease, thalassemiaNRBuCyMel, BuCy, CyTBI
      Baker et al
      Data from Machado et al.2
      , 1991
      63:326.5 (19-32)Germ cell cancersNRBuCy
      Ac, Actinomycin; Ad, Adriamycin; Ci, cisplatin; CTC, cyclophosphamide, thiotepa, carboplatin; Cy, cyclosphosphamide; Do, docetaxel; Ep, epirubicin; Le, letrozole; Mel, melphalan; NR, not reported; Pa, paclitaxel; TBI, total body irradiation; Vi, vincristine; VP16, etoposide; w/, with; w/o, without.
      Data from Machado et al.
      • Machado M.
      • Moreb J.S.
      • Khan S.A.
      Six cases of permanent alopecia after various conditioning regimens commonly used in hematopoietic stem cell transplantation.
      Data from Puglisi et al.
      • Puglisi F.
      • Aprile G.
      • Sobrero A.
      Tamoxifen-induced total alopecia.
      Figure thumbnail gr1
      Fig 1Clinical photograph of one of our docetaxel-induced permanent alopecia patients: diffuse-type alopecia characterized by sparse and thin hair all over the scalp.
      Ninety case reports of CIPAL were identified in the literature. These were associated with Bu and/or cyclophosphamide (Cy)–conditioning regimens used for bone marrow transplantation (BMT),
      • Park J.Y.
      • Choi Y.S.
      • Lee W.J.
      • Lee S.J.
      • Na G.Y.
      • Kim D.W.
      • et al.
      Five cases of permanent alopecia following chemotherapy.
      • Machado M.
      • Moreb J.S.
      • Khan S.A.
      Six cases of permanent alopecia after various conditioning regimens commonly used in hematopoietic stem cell transplantation.
      taxanes (docetaxel, paclitaxel),
      • Prevezas C.
      • Matard B.
      • Pinquier L.
      • Reygagne P.
      Irreversible and severe alopecia following docetaxel or paclitaxel cytotoxic therapy for breast cancer.
      tamoxifen
      • Puglisi F.
      • Aprile G.
      • Sobrero A.
      Tamoxifen-induced total alopecia.
      for breast cancer, and alfa-2a interferon (a-2a IFN) for essential thrombocythemia
      • Tornebohm-Roche E.
      • Merup M.
      • Lockner D.
      • Paul C.
      Alpha-2a interferon therapy and antibody formation in patients with essential thrombocythemia and polycythemia vera with thrombocytosis.
      (see Table I).
      The incidence of Bu/Cy-CIPAL ranged from 0.8% to 71% in adults and 24% in children.
      • Machado M.
      • Moreb J.S.
      • Khan S.A.
      Six cases of permanent alopecia after various conditioning regimens commonly used in hematopoietic stem cell transplantation.
      The male-to-female ratio was 1:1.2,
      • Park J.Y.
      • Choi Y.S.
      • Lee W.J.
      • Lee S.J.
      • Na G.Y.
      • Kim D.W.
      • et al.
      Five cases of permanent alopecia following chemotherapy.
      • Machado M.
      • Moreb J.S.
      • Khan S.A.
      Six cases of permanent alopecia after various conditioning regimens commonly used in hematopoietic stem cell transplantation.
      whereas the average age varied according to the age of the treated population. Forty-four percent of the children with Bu/Cy-CIPAL developed chronic graft-versus-host-disease.
      • Machado M.
      • Moreb J.S.
      • Khan S.A.
      Six cases of permanent alopecia after various conditioning regimens commonly used in hematopoietic stem cell transplantation.
      Bu/Cy-CIPAL occurred 7 to 27 months following BMT, showing 4 different clinical patterns: complete alopecia with or without facial hair loss, patchy alopecia, incomplete hair loss, and complete alopecia of the scalp, axillae, and pubic area.
      • Machado M.
      • Moreb J.S.
      • Khan S.A.
      Six cases of permanent alopecia after various conditioning regimens commonly used in hematopoietic stem cell transplantation.
      The onset of taxanes-CIPAL
      • Prevezas C.
      • Matard B.
      • Pinquier L.
      • Reygagne P.
      Irreversible and severe alopecia following docetaxel or paclitaxel cytotoxic therapy for breast cancer.
      in previously reported cases (median age, 56.5 years) was similar to that observed in our study. On examination, one patient had androgenic-type hair loss, and the other, diffuse alopecia of scalp and body hair.
      In tamoxifen-CIPAL (median age, 57.5 years), hair loss started 3 months after initiation of the treatment and was expressed as complete or androgenetic-type alopecia.
      • Puglisi F.
      • Aprile G.
      • Sobrero A.
      Tamoxifen-induced total alopecia.
      Alfa-2a IFN-CIPAL has been reported to be 1 in 10. In this report the onset of hair loss was not reported but was described as being complete.
      • Tornebohm-Roche E.
      • Merup M.
      • Lockner D.
      • Paul C.
      Alpha-2a interferon therapy and antibody formation in patients with essential thrombocythemia and polycythemia vera with thrombocytosis.
      Histopathologic findings of the Bu/Cy-CIPAL cases described reduced numbers of hair follicles without increase in telogen or vellus follicles
      • Machado M.
      • Moreb J.S.
      • Khan S.A.
      Six cases of permanent alopecia after various conditioning regimens commonly used in hematopoietic stem cell transplantation.
      and that of taxanes-related cases
      • Prevezas C.
      • Matard B.
      • Pinquier L.
      • Reygagne P.
      Irreversible and severe alopecia following docetaxel or paclitaxel cytotoxic therapy for breast cancer.
      was similar to our findings. No biopsies were performed on patients with tamoxifen-CIPAL
      • Puglisi F.
      • Aprile G.
      • Sobrero A.
      Tamoxifen-induced total alopecia.
      and a-2a IFN-CIPAL.
      • Tornebohm-Roche E.
      • Merup M.
      • Lockner D.
      • Paul C.
      Alpha-2a interferon therapy and antibody formation in patients with essential thrombocythemia and polycythemia vera with thrombocytosis.
      Risk factors for CIPAL related to taxanes and a-2a IFN have not been identified.
      • Prevezas C.
      • Matard B.
      • Pinquier L.
      • Reygagne P.
      Irreversible and severe alopecia following docetaxel or paclitaxel cytotoxic therapy for breast cancer.
      • Tornebohm-Roche E.
      • Merup M.
      • Lockner D.
      • Paul C.
      Alpha-2a interferon therapy and antibody formation in patients with essential thrombocythemia and polycythemia vera with thrombocytosis.
      Tamoxifen-CIPAL seems to occur in genetically susceptible patients.
      • Puglisi F.
      • Aprile G.
      • Sobrero A.
      Tamoxifen-induced total alopecia.
      Following the conditioning regimes for BMT, risk factors for CIPAL in adults included dose intensity, different bioavailability of the drugs, female sex, older age in males, allogenic BMT and in children, chronic graft-versus-host-disease, older age, and previous cranial radiotherapy.
      • Machado M.
      • Moreb J.S.
      • Khan S.A.
      Six cases of permanent alopecia after various conditioning regimens commonly used in hematopoietic stem cell transplantation.
      There is no current effective therapy for CIPAL. However, we recommend appropriate counseling before and after chemotherapy where patients are treated with these agents.
      We thank Professor David Thomson and Dr Penelope Thomson for kindly editing the manuscript.

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