Dermoscopic Follow-Up of the Skin towards Acute Graft-versus-Host-Disease in Patients after Allogeneic Hematopoietic Stem Cell Transplantation.

Background. Acute graft-versus-host disease (aGVHD) involving skin is one of the most frequent complications of allogeneic hematopoietic stem cell transplantation (alloHSCT), usually diagnosed based on clinical manifestations. So far, skin biopsy with histopathological evaluation is the only method to confirm the diagnosis. Objective. In this prospective study we monitored alloHSCT recipients by dermoscopy in order to assess its utility as an alternative noninvasive tool to early diagnose acute GVHD. Methods. Thirteen consecutive patients who received alloHSCT were examined clinically and dermoscopically towards aGVHD [days 28 (±7), 56 (±7), and 100 (±7)], as well as in each patient who developed cutaneous aGVHD diagnosed according to clinical criteria (Glucksberg scale). Results. Six patients (46%) developed symptoms of cutaneous acute GVHD (grade 1, n = 3; grade 2, n = 3). Dermoscopic evaluation revealed pinkish or reddish background and well-visible, multiple thin telangiectasias. Conclusion. To our knowledge, this is the first report on the use of dermoscopy to evaluate skin involvement in the course of acute GVHD suggesting its role as a diagnostic tool in follow-up of GVHD, which can be also used before clinical symptoms occur.

Acute graft-versus-host disease. The incidence and risk factors.

OBJECTIVES: Acute graft-versus-host-disease (aGvHD) is a major cause of mortality after allogeneic hematopoietic cell transplantation (alloHCT). The goal of this study was to evaluate the incidence and risk factors for this complication. METHODS: 330 consecutive patients (183 male and 147 female), aged 29 (10-56) years, treated with alloHCT in a single center between 1992-2003 were included in the analysis. AlloHCT was performed after myeloablative conditioning from either related donor (rel-HCT) (n=223) or unrelated voulnteer (URD-HCT) (n=107). GVHD prophylaxis consisted of cyclosporin, methotrexate +/- prednisolone. RESULTS: Cumulative incidence of grade II-IV and grade III-IV aGvHD equaled 31% and 17%, respectively. In multivariate analysis the following factors were associated with increased risk of grade II-IV aGvHD: the diagnosis of chronic myeloid leukemia (CML) or myelodysplastic syndrome (MDS) (vs. other diagnoses), URD-HCT (vs. Rel-HCT), years of alloHCT 1992-2001 (vs. 2002-2003), donor age > or =35 years, and CD34+ cell dose > or = 4.0 x 10(6)/kg. Increased risk of grade III-IV aGVHD was associated with: the use of prednisolone for aGvHD prophylaxis, the diagnosis of CML or MDS, and CD3+ cell dose > or =100 x l0(6)/kg. CONCLUSIONS: Incidence of aGvHD depends on various recipient-, donor-, and procedure-related factors. This should be taken into account when planning treatment for every individual patient.

[A study to determine the safety and efficacy of imatinib mesylate in patients with chronic phase of chronic myeloid leukemia after interferon therapy failure. Four year follow-up]. / Ocena skutecznosci i bezpieczenistwa stosowania imatinibu mesylate u pacjentów z faza przewlekla przewleklej bialaczki szpikowej po niepowodzeniu leczenia interferonem 4 lata obserwacji.

UNLABELLED: Targeted therapy with the use of imatinib mesylate is a recognized option for patients with chronic myeloid leukemia (CML) not eligible for allogeneic hematopoietic cell transplantation. We present results of a multicenter phase II study on the use of imatinib in chronic phase after failure to interferon-alpha (IFN-alpha). Sixty patients (27 female, 33 male), median age 46 (range, 21-64), were included with hematologic relapse (n= 11), hematologic refractoriness (n=4), cytogenetic relapse/ /+65resistance (n=40) or intolerance to IFN-alpha (n=5). The median time from CML diagnosis was 39 months (range, 4-132), the median time of IFN-alpha therapy equaled 23 months (range, 1-78). Imatinib mesylate was administered at a dose of 400 mg/day for 1 year. In patients who achieved major cytogenetic response (MCR) the therapy was continued until progression. Thirty-three (55%) patients achieved MCR after one year of treatment. At 4 years the cumulative incidence of complete cytogenetic response equaled 40% (95% CI, 29-56). Among 27 patients who did not achieve MCR at 12 moths, in 12 cases the study course was discontinued prematurely because of blast crisis (n=9), prolonged neutropenia (n=l), severe transaminases elevation (n=l) or incidental death not related to the study drug or disease (n=l). The probability of OS at 4 years equaled 82% (95% CI, 72-91) and was lower for patients with the disease duration >36 months and those with Sokal index > or =0.8. Among patients who achieved MCR, the probability of progression-free survival was 78% (95% CI, 69-85). Time to progression (cytogenetic, n=6; blast crisis, n=l) varied from 3-36 months. CONCLUSIONS: Imatinib mesylate is characterized by good tolerance and allows achieving cytogenetic response in more than half of late chronic phase CML patients with failure of interferon therapy. However, the progression rate is substantial, which raises concern regarding the curative potential of monotherapy with imatinib in this group of patients.

Successful treatment of pure red cell aplasia with repeated, low doses of rituximab in two patients after ABO-incompatible allogeneic haematopoietic stem cell transplantation for acute myeloid leukaemia.

We describe two patients with acute myeloid leukemia successfully treated with anti-CD20 antibody for pure red cell aplasia (PRCA) following ABO-mismatched allogeneic hematopoietic stem cell transplantation (HSCT). PRCA following HSCT is associated with major ABO incompatibility between donor and recipient and is due to an inhibition of donor erythroid precursors by residual host isoagglutinins. The first patient developed PRCA resistant to several treatment options including donor-derived leukocyte infusions (DLI), high-dose erythropoietin (EPO), and rapid tapering of cyclosporin A (CsA). This patient also received anti-viral therapy as CMV and parvovirus B19 infections were regarded as additional causes of PRCA. Due to a loss of donor chimerism, he underwent second HSCT, but PRCA still persisted. He showed no evidence of graft-versus-host disease (GVHD). Finally he was administered anti-CD20 antibody (rituximab) at a dose of 150/m2 and PRCA resolved in a short period of time. The case was complicated by life-threatening pulmonary aspergillosis with septic shock, successfully treated with anti-fungal therapy. The second case concerns a patient, who revealed PRCA after major ABO-incompatible HSCT from his brother. Considering our experience with the previously described patient, he proceeded to rituximab at a dose of 150/m2 as first line treatment. We observed rapid recovery from PRCA without any side effects. We conclude that rituximab seems to be a promising therapeutic option in patients with PRCA after ABO-mismatched HSCT, in whom conventional treatment fails.

The impact of immunosuppressive therapy on an early quantitative NK cell reconstitution after allogeneic haematopoietic cell transplantation.

OBJECTIVES: The goal of this study was to examine the impact of various immunosuppressive regimens on an early NK cell recovery following haematopoietic cell transplantation (alloHCT). METHODS: The number of peripheral blood NK cells was analysed with the use of flow cytometry on day +30 (+/-2) after alloHCT from an HLA identical sibling (n=43) or an unrelated (n=34) donor. RESULTS: Patients receiving prednisolone as a prophylaxis of acute graft-versus-host disease had lower number of NK cells compared to those not given steroids prophylactically (110(10-694) vs. 212(33-890) x 10(6)/L, p = 0.005). In contrast, administration of anti-thymocyte globulin (ATG) (7.5-15 mg/kg) as a part of preparative regimen was not found to influence the NK cell recovery. Similarly, no effect on the number of peripheral blood NK cells was observed with regard to other analysed factors: cell dose, type of myeloablative conditioning, source of stem cells, patient and donor characteristics, number of post-transplant methotrexate doses. CONCLUSIONS: Immunosuppressive therapy may affect NK cell recovery following alloHCT. Since NK cells are considered a potential tool for cellular therapy of haematological malignancies, our findings should be taken into account when planning this kind of treatment in the context of allotransplantation.