[Clinical observation of mesenchymal stem cell as salvage treatment for refractory acute graft-versus-host disease].

OBJECTIVE: To explore the effect of mesenchymal stem cells (MSCs) on refractory acute graft-versus-host disease (GVHD) failed to second-line immunosuppressive therapy. METHODS: Twenty-two patients with refractory aGVHD received the treatment of first- and/or second-line immunosuppressive agents in combination with MSCs. The MSCs from bone marrow (BM) of HLA-unrelated third-party donors, were used at the median time of 19 (11 - 49) days after aGVHD onset, at a dose of 1×10(6)/kg once with an interval of 14 days. If the symptoms of aGVHD did not improve after continuous infusion four times, MSCs would be discontinued. Meanwhile the proportion of CD3(+)CD4(+), CD3(+)CD8(+) and CD4(+)CD25(+) was detected by flow cytometry (FCM) before and 4 weeks after the MSCs infusion. RESULTS: The median dose of MSC was 4.8 (2.5 - 6.3)×10(6) cell×kg(-1) with a median infusion of 2.5 (1 - 7) times per case. Twelve patients achieved complete response (CR), four partial response (PR) after treatment. The total effective rate was 72.7% (16/22). With a median follow-up of 246.5 (36 - 1116) days post-transplantation, 11 patients survived and 11 died. The causes of death included GVHD(n = 6), infections (n = 3), leukemia relapse (n = 1) and post-transplant lymphoproliferative diseases (n = 1), respectively. The proportion of CD3(+)CD4(+)/CD3(+)CD8(+) was significantly higher at 4th week after MSCs infusion compared to before infusion (1.58 ± 0.54 vs 0.49 ± 0.19, \%t\% = 0.628, P = 0.04). The number of CD4(+)CD25(+) Treg cells had not changed much compared to before infusion (P = 0.606). CONCLUSION: MSCs derived from the BM of a third-party donor are effective to treat aGVHD failed to second-line immunosuppressive therapy after allo-HSCT. MSCs might play a role in aGVHD by regulating the rate of CD3(+)CD4(+)/CD3(+)CD8(+).

[A clinical study of chronic disseminated candidiasis in patients with acute leukemia].

OBJECTIVE: To deepen the understanding of chronic disseminated candidiasis (CDC) in patients with acute leukemia (AL). METHODS: CDC was investigated in 119 AL patients who received induction chemotherapy from August 2004 to May 2005. Clinical manifestations, laboratory tests, imaging modalities, diagnosis and treatment were investigated retrospectively. RESULTS: Three patients (2.5%) were identified to be suffering from CDC. All the three patients had an absolute neutrophil count (ANC) <0. 5 x 10(9)/L for more than 15 days. Two patients had normal ANC when they were diagnosed to have CDC. The common manifestations in these three patients were persistent fever, splenohepatomegalia and percussion pain in hepatic region. Meanwhile, 2 of them were accompanied with cough, expectoration and dyspnoea. The abnormal laboratory test observed during the course of infection in two of them was increase of alkaline phosphatase. Computed tomography scan showed multiple hypodense lesions in the liver and spleen in all the three patients; two of them showed multiple nodular patchy shadows in lungs. Nuclear magnetic resonance imaging showed multiple abnormal signal in liver, spleen and kidneys in one of the patients. Two patients had positive bleed fungal cultures and histologic examination in one of the patients were positive for Candida tropicalis. Two patients received amphotericin B therapy empirically, but it was replaced by amphotericin B colloid dispersion (ABCD) later in one and combined with voriconazole in another because of unresponsiveness to the drug. One patient took a favorable turn after receiving ABCD therapy for 45 d, which was replaced by voriconazole because of the emergence of fever after discontinuation of ABCD. All the three patients received further chemotherapy smoothly after the diagnosis of CDC. CONCLUSION: The diagnosis of CDC remains difficult. Fungal blood cultures and histologic examination have been considered in many studies as the golden standard for the diagnosis of CDC. Amphotericin B is the cornerstone of treatment in patients with CDC and lipid formulations of amphotericin B can be used in CDC patients who are intolerant of or refractory to conventional amphotericin B. Voriconazole has a favorable response for refractory/relapse patients and could be used for second line treatment. The development of CDC in patients with acute leukemia does not preclude further chemotherapy.