Resolution of psoriasis after allogeneic bone marrow transplantation for chronic myelogenous leukemia: late complications of therapy

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Treatment of autoimmune disease with bone marrow transplantation (BMT) is under investigation. A few reports of patients undergoing allogeneic BMT for malignant conditions observed the resolution of psoriasis after BMT, with minimal late morbidity. We describe a patient with chronic myelogenous leukemia (CML) whose psoriasis resolved completely after allogeneic BMT. However, the patient's course was complicated by extensive chronic graft-versus-host disease (GVHD), recurrent serious infections, poor performance status and quality of life, and severe disability. The patient died 887 days post transplant due to infectious complications. The potential benefits and risks of treatment of autoimmune diseases with allogeneic BMT are discussed. Bone Marrow Transplantation (2000) 26, 1239–1241.


Psoriasis is one of the most common dermatologic diseases, affecting more than six million people in the United States and up to 2% of the world's population.1 Psoriasis is a chronic inflammatory disease exhibiting a wide spectrum of clinical signs ranging from variable skin manifestations to debilitating arthritis. Disease affecting younger patients is generally more severe and recurrent. Treatment strategies include the use of a combination of emollients, corticosteroids, vitamin-D analogues, cyclosporine, tar preparations, dithranol, PUVA and retinoids.

Psoriasis is an immune-mediated disease. Activated CD4+ and CD8+ lymphocytes infiltrate the dermis and epidermis, resulting in hyperkeratosis, parakeratosis, epidermal acanthosis and elongation of rete ridges, and vascular dilatation.12 With T cells an important component in the pathogenesis of psoriasis, ablation of the recipient lymphoid compartment and infusion of allogeneic bone marrow is a treatment strategy which may have curative potential. Indeed, in animal models, allogeneic (and autologous) BMT has been shown to favorably alter the course of certain immune-mediated diseases.3 Also, several clinical case reports demonstrated durable resolution of psoriasis after allogeneic BMT performed for concurrent malignant conditions.45678 These reports did not observe significant late procedure-related morbidity.

In this report, we describe a patient with long-standing, extensive psoriasis poorly responsive to conventional treatments which resolved completely through 2.4 years of follow-up after an allogeneic BMT, performed for the diagnosis of CML. This case report demonstrates that long-term remission of immune-mediated diseases can occur with allogeneic BMT, but also illustrates the potentially serious risks associated with the application of this treatment strategy to patients with autoimmune diseases.

Case report

A 55-year-old woman underwent allogeneic BMT in 1996, 4 months following a diagnosis of CML. The bone marrow donor was her healthy HLA matched brother. The patient also had a history of long-standing severe erythrodermic psoriasis for 33 years, which manifested as typical, well demarcated erythematous scaling plaques, symmetrically distributed over the elbows, knees, trunk and buttocks. During the years preceding the transplant, the patient was treated with multiple therapeutic regimens including corticosteroids, tar preparations, emollients, PUVA and methotrexate, but with no significant response. Immediately before allogeneic BMT, the patient's physical examination was notable for psoriatic skin plaques, involving more than two thirds of her body surface area (Figure 1).

Figure 1

Psoriatic skin plaques present on the left hand of the patient just before start of conditioning regimen for allogeneic BMT

The conditioning regimen for allogeneic BMT included busulfan (1 mg/kg every 6 h for 16 doses) and cyclophosphamide (60 mg/kg/day for 2 days), followed by transplantation of unmanipulated fresh bone marrow cells collected from her HLA-identical sibling. The bone marrow contained 1.71 × 106/kg CD34+ cells and 1.51 × 107/kg CD3+ cells. Cyclosporine and methylprednisolone were given for GVHD prophylaxis. On day +30, the patient had complete engraftment of donor cells and complete remission of CML, as determined by analysis of variable number of tandem repeats (VNTR) and cytogenetics, respectively.

The patient's extensive psoriatic plaques responded rapidly after initiation of the conditioning regimen, were only faintly visible on the day of transplantation (Figure 2), and resolved completely by day +7. The response of the psoriatic skin plaques was durable, with no evidence of recurrence of psoriasis through 2.4 years of follow-up post transplant.

Figure 2

Picture of the patient's left hand obtained on the day of transplantation, demonstrating rapid response of the psoriatic skin plaques after initiation of the conditioning regimen.

Multiple serious treatment-related complications occurred following the allogeneic BMT. During the first 6 months post transplant, the patient developed separate episodes of culture-negative febrile neutropenia, catheter-related infections, Enterobacter species bacteremia, and CMV pneumonitis. Each of these complications required hospitalization, but resolved after appropriate therapy. Prolonged cytopenia also occurred due to myelosuppression related to immunosuppressive medications, recurrent infections, and chronic GVHD.

Acute and chronic GVHD were significant transplant-related complications for the patient. Acute GVHD (grade 2, skin only) developed early post transplant, and responded to increasing doses of corticosteroids. Chronic GVHD of the progressive type subsequently developed, in association with thrombocytopenia (platelet count <100 000/μl). Despite aggressive immunosuppressive treatment with cyclosporine, corticosteroids, and azathioprine, significant involvement of the skin, oral and eye mucous membranes, gastrointestinal tract and liver persisted.

The patient's quality of life was poor throughout the entire post-transplant course, with a performance status (ECOG) of 3. Manifestations of poor quality of life included diffuse weakness due to severe proximal myopathy from chronic corticosteroid use, pain due to chronic oral buccal mucosal GVHD, poor nutrition due to oral and esophageal involvement by chronic GVHD, and multiple hospitalizations due to recurrent infections. As a result of these complications, the patient was unable to work during the entire post-transplant course.

During the final 3 months of the patient's life, the chronic GVHD was poorly responsive to therapy. The patient expired 887 days post transplant as a result of lobar pneumonia and acute renal failure.


Case reports have described the complete and durable resolution of psoriasis following allogeneic BMT given for treatment of co-existing malignancy, with minimal late procedure-related morbidity.45678 This case report adds to this limited body of literature. Our patient's psoriasis resolved early following allogeneic BMT and remained in remission through 2.4 years of follow-up. The rapidity of response with near complete resolution of the psoriatic skin lesions by the day of transplant suggest that the conditioning regimen contributed substantially to the early response of the disease. The immunosuppressive therapy given to treat GVHD may have also contributed to the remission of the psoriasis. As observed in other case reports,4567 the response of the patient's psoriasis to allogeneic BMT was durable, lasting in excess of 2 years. Recurrence of psoriasis following allogeneic BMT was reported in only one patient;8 however, this seemingly high efficacy should be cautiously interpreted as the overall number of reports is low.

High-dose therapy and BMT is increasingly being used as a research strategy for treatment of selected patients with autoimmune diseases.3 Allogeneic BMT has led to durable remission of autoimmune disease in most patients, but the number of reports is small and the potential risks of the procedure are high. Autologous BMT has also resulted in disease remissions. Of interest, passive transfer of autoimmune disease with allogeneic BMT has been reported.7

Although some patients with autoimmune disease appear to have benefitted from BMT, the potential risks of this intensive treatment must be balanced with the efficacy, and with the outcomes of similar patients not treated with BMT. The early toxicity of BMT can be substantial. Thus, several investigators recommended autologous over allogeneic BMT in these patients because of the lower treatment-related morbidity and mortality (TRM) of the former procedure when used to treat patients with malignant diseases.3 However, even autologous BMT is associated with substantial risk of early toxicity, with a reported TRM of 9% when used to treat patients with autoimmune diseases.9 This TRM approaches that recently observed with some low intensity or non-myeloablative conditioning regimens used for matched related donor transplantation,10 suggesting that the latter may be a reasonable option for some patients, especially those whose autoimmune disease may be genetically determined.

Most reports to date of patients with autoimmune diseases undergoing BMT focused on early toxicities of BMT, with little or no comment on late complications of transplant. This case report illustrates some of the long-term risks of allogeneic BMT used to treat CML in a patient with a co-existing autoimmune disease. Our patient developed extensive chronic GVHD which never completely responded to aggressive treatment. Manifestations of GVHD including buccal mucosal pain and poor nutrition, poor vision due to conjunctivitis, and reduced performance status resulted in substantial morbidity and complete work disability. Complications of immunosuppressive therapy given to treat the GVHD included severe steroid myopathy and recurrent infections, the latter of which ultimately contributed to the patient's death 2.4 years post transplant. While these problems may be unique to patients who undergo allogeneic transplant, the increasing use of manipulated autologous stem cell transplants in these patients should also be of concern because of the possibility of delayed or incomplete immune reconstitution. Thus, patients with autoimmune disease who receive manipulated autologous stem cells should also be followed long-term to characterize the late risks of this procedure.

This case report, like others, demonstrates that long-term remission of immune-mediated diseases can occur with BMT, but also illustrates the potential serious late risks associated with the application of this treatment strategy to patients with autoimmune diseases. In addition to the primary endpoints of efficacy and early toxicity assessments, clinical research trials evaluating the BMT treatment strategy in patients with autoimmune disease should seek to carefully characterize the late risks of this treatment. Efficacy, and early and late toxicity must be understood to define the ultimate role, if any, of high-dose therapy and BMT in the treatment of patients with autoimmune diseases.


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Adkins, D., Abidi, M., Brown, R. et al. Resolution of psoriasis after allogeneic bone marrow transplantation for chronic myelogenous leukemia: late complications of therapy. Bone Marrow Transplant 26, 1239–1241 (2000) doi:10.1038/sj.bmt.1702703

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  • autoimmunity
  • psoriasis
  • bone marrow transplantation

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