Radiotherapy-based conditioning is effective immunosuppression for patients undergoing transplantation with T-cell depleted stem cell grafts for severe aplasia.

BACKGROUND: We studied the outcome of individuals with aplastic anemia conditioned with a radiation-containing regimen followed by an infusion of stem cell grafts that had been depleted of lymphocytes with CAMPATH-1H (antiCD52; humanised). METHODS: The conditioning regime consisted of fractionated (f) TBI 8 Gy followed by f total nodal irradiation (TNI) 6 Gy. In addition, patients received CY 60 mg/kg on 2 consecutive days. Cytokine-mobilized peripheral blood grafts from HLA-identical siblings were T-cell depleted with CAMPATH-1H 'in the bag'. CsA was commenced on day -1 and continued until day +90. RESULTS: Seventeen heavily transfused patients with aplastic anemia, median age 18 years (range 14-56 years), were studied. The median time from diagnosis to transplantation was 172 days (range 34-443 days). The median CD34(+) cell number infused was 3.47 x 10(6)/kg (range 1.03-18.4 x 10(6)/kg). All patients engrafted. Recovery was fast and patients reached 0.5 x 10(9)/L polymorphs by median day 11 (range 9-17 days). Toxicity from the conditioning included grade 4 hematologic toxicity in all patients. Another major toxicity was gastrointestinal mucosal damage, which exceeded grade 2 in two instances. One patient developed thrombotic thrombocytopenic purpura, which responded to substitution of CsA with tacrolimus and plasmapheresis. Another patient, who had normal blood counts, died of infection on day 241. Chimerism studies at 6 months post-transplantation confirmed the donor origin of hematopoiesis in all seven patients tested. None of the patients developed acute or chronic GvHD. There was no delayed graft failure and 94% of patients had survived disease free at a median of 1303.5 days (range 216-2615 days) from graft infusion. DISCUSSION: In this cohort of multiply transfused patients, the radiation-containing schedules described in this study led to universal engraftment with limited toxicity despite T-cell depletion. No patient developed GvHD or late graft failure. Lower doses of radiation-containing conditioning should be explored further.

Intensified myeloablative therapy and autologous stem-cell transplantation for patients with AML: single center experience.

BACKGROUND: Thirty-seven consecutive individuals in CR of AML received intensified conditioning and autologous stem-cell transplantation. METHODS: For those receiving PBSC (n = 28), mobilization protocol was with cyclophosphamide 60 mg/kg followed by G-CSF injection at 5-10 microg/kg; stem cells were harvested by large volume apheresis (6-8 blood volumes) and then cryopreserved. Ablative therapy consisted of fractionated TBI (total 12 Gy), followed by four fractions (1.5 Gy each) of total nodal irradiation (TNI), and CY 120 mg/kg under mesna cover. RESULTS: For individuals transplanted in CR 1 (n = 31) the median time from diagnosis to grafting was 167 (range 92 - 212) days. Patients transplanted with PBSC received high number of CFU-GM x 10(4)/kg (P < 0.01), a difference that was associated with a significantly shorter platelet recovery. While there was no early transplant-associated mortality, in 10 patients death was caused by recurrence of the disease. The median survival is 1746 (range 105-4467) days and 26 (70%) survive disease free, at a median 2207 (range 698-4467) days from transplantation. Multivariate analysis showed that survival of patients with AML-M3, receiving higher CFU-GM (P = 0.04) and without morphological dysplasia (P = 0.01) was longest. DISCUSSION: For patients in remission of AML, transplantation with PBPC appears to be an effective form of intensification, particularly when TBI + TNI (delivering a total of 18 Gy to the axial skeleton) were used as conditioning.

The detection of circulating melanoma cells correlates with tumour thickness and ulceration but is not predictive of metastasis for patients with primary melanoma.

We analysed peripheral blood samples from 143 patients with primary melanoma (PM) for the presence of tyrosinase mRNA by reverse transcription-polymerase chain reaction (PCR) to determine whether the early detection of circulating melanoma cells (CMCs) is of clinical value in monitoring melanoma progression. Ten of the patients (7%) with PM had detectable CMCs. The percentage of PCR-positive patients was higher for stage II patients (9.0%) than for stage I (5.3%), but the difference was not significant. A significantly higher percentage (P<0.05) of PCR-positive patients were found to have tumours greater than 1.5 mm in thickness or had ulcerated tumours. This suggests that tumour thickness and ulceration are the two most significant prognostic factors. The detection rate of 9% for patients with stage II disease is much lower than would be expected, since 23.9% (16 out of 67) of the stage II patients subsequently developed metastases. Of these 16 patients, only one was PCR-positive, 1 week before the metastases became clinically evident. Thus, the current technique fails to predict the likelihood of developing metastatic disease (P=0.3485). The other nine PCR-positive patients had not developed metastases after a median follow-up period of 4 years. It is concluded that this technique for the detection of CMCs is of limited clinical value in predicting the likelihood of metastasis in patients with PM. It is suggested that the detection of micrometastases in other anatomical compartments, such as sentinel lymph nodes, should be explored for the identification of patients at risk for developing metastases.

Plantar melanoma: results of treatment in three population groups.

BACKGROUND: The frequency of plantar melanoma varies widely in different population groups. The plantar surface is an infrequent site in white persons but is common in the black population. The effect of ethnicity on melanoma of the plantar surface has not previously been well defined. The aim of this study was to analyze the results of a standard protocol of treatment of melanoma of the sole in 3 homogeneous population groups treated during a 15-year period at a university referral hospital. METHODS: A retrospective analysis of 1403 consecutive patients with melanoma treated between 1977 and 1991 was performed. Eighty-five patients (35 black, 25 white, and 16 of mixed ancestry) had primary cutaneous melanoma involving the sole of the foot. RESULTS: Acral lentiginous melanoma was the most common histogenetic type and occurred in 49 patients. Significantly more black patients (20 of 35) had metastatic disease compared with white patients or groups with mixed ancestry (P < .05). The Breslow depth was significantly more advanced in black patients (7.1 mm) with stage I disease than in white patients (3.3 mm) or those of mixed ancestry (3.6 mm) (P < .05). The 5-year survival rate was 60% for white patients, 26% for black patients, and 24% for those of mixed ancestry. CONCLUSIONS: Black patients were seen more frequently with advanced local disease, and nearly half had disseminated disease. Those of mixed ancestry had a histogenetic type resembling that of black patients, but the Breslow depth of penetration was similar to that of white patients. Education programs to heighten awareness of both patient and physician are required to enable earlier diagnosis and improve outcome.