Toxic erythema of chemotherapy following i.v. BU plus fludarabine for allogeneic PBSC transplant.

I.v. BU plus fludarabine is an effective conditioning regimen for myeloid neoplasias with low treatment-related mortality. At standard doses, cutaneous toxicity has been reported in <5% of cases. As we observed a much higher incidence of cutaneous toxicity in patients who received predominantly pharmacokinetically based doses of BU, we performed a retrospective analysis of 61 patients who received i.v. BU plus fludarabine (+/- antithymocyte globulin; ATG) as a conditioning regimen before allogeneic PBSC transplant. Of the 58 evaluable patients, 33 (57%) developed cutaneous toxicity that fell within the spectrum of toxic erythema of chemotherapy (TEC). The median onset of TEC was 22 days and most patients had multiple sites of involvement, with the groin, axillae and palms/soles being the favored sites. In men, scrotal involvement, sometimes severe, was also commonly observed. Initially, allergic reactions to antibiotics, fungal infections and GVHD were also considered until the clinical presentation of TEC became well recognized. In all patients, the skin healed without specific therapy but resolution often required several weeks. This series suggests that TEC is common after BU/fludarabine+/- ATG and it is important for transplant physicians to recognize, particularly as misdiagnosis could lead to inappropriate treatment.

A simplified approach to stem cell mobilization in multiple myeloma patients not previously treated with alkylating agents.

High-dose chemotherapy and autologous stem cell rescue is considered a standard part of initial therapy for patients with multiple myeloma. Therefore, potential transplant candidates are generally treated with dexamethasone-based programs rather than alkylating agents to avoid stem cell toxicity. The optimal mobilizing regimen for patients with multiple myeloma has not been defined. However, aggressive chemotherapy may result in excessive morbidity and cost in this older, immunocompromised population. We retrospectively examined our experience with a well-tolerated regimen of 1.5 g/m(2) cyclophosphamide on day -10 followed by 10 microg/kg G-CSF beginning on day -7 in 50 consecutive patients with multiple myeloma and no prior alkylating agent therapy. Median stem cell collection was 4.88 x 10(6) CD34+ cells/kg per apheresis and 44 patients collected >5 x 10(6) CD34+ cells/kg within 2 days. In 36 patients, more than 10 x 10(6) CD34+ cells/kg were collected including 33 patients who required 1-2 days of collection. One patient required hospitalization for fever/neutropenia and two required weekend apheresis. We conclude that 1.5 g/m(2) cyclophosphamide plus 10 microg/kg G-CSF is a safe, effective, highly predictable mobilizing program that uniformly provided enough stem cells for one transplant and enough stem cells for two transplants.

Chronic graft-versus-host disease of the liver: presentation as an acute hepatitis.

Chronic graft-versus-host disease (GVHD) of the liver usually presents as an indolent cholestatic disease in patients with skin, mouth, and eye involvement. We observed 14 patients in whom chronic GVHD of the liver presented with marked elevations of serum aminotransferases, clinically resembling acute viral hepatitis. Onset of liver dysfunction was at 294 days (range, 74-747 days) after allogeneic hematopoietic cell transplantation and coincided with a recent cessation or taper of immunosuppressive drugs. Median peak serum alanine transaminase (ALT) was 1,640 U/L (698-2,565 U/L), and median bilirubin was 12.3 mg/dL (0.9-55.9 mg/dL). All biopsies showed characteristic features of GVHD with damaged and degenerative small bile ducts. Other features included a marked lobular hepatitis, moderate to marked amounts of hepatocyte unrest, sinusoidal inflammation with perivenular necroinflammatory foci, and many acidophilic bodies scattered throughout the lobule. When high-dose immunosuppressive therapy was instituted soon after presentation, progressive improvement and eventual normalization of liver enzymes and bilirubin levels were observed. However, in cases in which the diagnosis was not made and therapy was delayed, a progressive cholestatic picture emerged with histologic evidence of loss of small bile ducts and portal fibrosis. We conclude that a distinct syndrome of chronic liver GVHD presenting as an acute hepatitis can be recognized in a patient at risk who is receiving no, or minimal, immunosuppressive medications. Liver biopsy is necessary to exclude viral causes of liver dysfunction and to confirm characteristic abnormalities of small bile ducts. Institution of high-dose immunosuppression can prevent progressive bile duct destruction and effect resolution of jaundice if given early.