Refractory thrombotic thrombocytopenic purpura: successful treatment by plasmapheresis with plasma cryosupernatant.

BACKGROUND: Plasma exchange (PE) with reinfusion of fresh frozen plasma (FFP) is the therapy of choice for thrombotic thrombocytopenic purpura (TTP) in the acute phase. About 20% of patients do not respond fully to this treatment and can suffer relapse. The plasma cryosupernatant (PCS) fraction depleted of the largest von Willebrand factor (vWF) multimers, considered to be among the possible causes of relapse, has recently been suggested as an alternative to FFP. METHODS: We submitted three patients in TTP relapse to plasma exchange with reinfusion of PCS. This treatment was associated with anti-platelet agents in two of the patients. RESULTS: Infusion of PCS led to a rapid improvement of the clinical picture in all three patients, with a return to normal of the reference parameters (platelet count' serum LDH). A few days after suspending PE, the patient not receiving anti-platelet treatment suffered another relapse which was definitively resolved with resumption of PE and administration of anti-platelet agents. CONCLUSIONS: We consider PCS to be a valid alternative treatment for TTP relapses, and we have found that the best results are obtained when it is associated with anti-platelet agents.

Terminal deoxynucleotidyl transferase-positive acute leukemias evolving from a myelodysplastic syndrome.

We have analyzed the distribution of terminal deoxynucleotidyl transferase (TdT) in 30 patients with myelodysplastic syndromes (MDS), in connection with morphology, cytochemistry, and cytogenetics. All cases in preleukemic phase were strictly TdT-negative. At variance, 4 (19%) of 21 cases with subsequent leukemia were TdT-positive and showed a pure lymphoid (one case) or a mixed lymphoid-myelomonocytic (three cases) morphology. The TdT enzymatic activity ranged from 2 to 21 U/10(8) cells and the percent of positive cells in the immunofluorescence test ranged from 10 to 80% of total. All cases were Philadelphia chromosome-negative. The clonal origin of MDS from the pluripotent stem cell, capable of originating both a lymphoid and myeloid progeny, is further corroborated.

Immunoblastic lymphoma: a clinicopathologic study with emphasis on the cases intervening during or following other disorders.

Fifty-eight patients with immunoblastic lymphoma (IBL) were the object of this study. Fifteen of them (26%) developed IBL during or after other diseases, either immunologic or neoplastic, including angio-immunoblastic lymphadenopathy, autoimmune disorders, chronic lymphocytic leukemia, Waldenström's disease, lymphoplasmacytoid lymphoma and Hodgkin's disease (subsequent IBL). The comparison between de novo and subsequent IBL revealed a significantly higher incidence of bone marrow involvement and bulky abdominal disease in the latter group, with a lower response rate to chemotherapy. The favorable primary extranodal disease of Waldeyer's ring exclusively belonged to de novo IBL, whereas the frequency of immunoglobulin abnormalities was higher in the subsequent IBL group (67%). The stage of disease, systemic symptoms at diagnosis and response to therapy were predictive of survival. The overall complete remission (CR) rate in the whole series was 37% and the median overall survival 14 months. Complete remitters have a median survival in excess of 60 months; all relapses occurred within the first 12 months of CR. No CNS relapse terminated the CR, and CNS prophylaxis seems unnecessary in IBL. The analysis of subsequent IBL may provide information on the pathogenesis of non-Hodgkin's lymphomas; the still poor prognosis of IBL deserves new therapeutic attempts to improve on the standard regimens.

Lymphoblastic lymphoma in adults: a study on 30 patients treated with two different programs according to bone marrow findings.

Thirty adult patients with lymphoblastic lymphoma were treated with two different programs according to bone marrow findings. Bone marrow positive patients were given an ALL-like program: vincristine, daunorubicin, cyclophosphamide and prednisone for induction of remission, CNS prophylaxis, continuous maintenance for three years and monthly reinductions. Bone marrow negative patients were given a conventional lymphoma program with CHOP-Bleo and limited RT on bulky mediastinum without CNS prophylaxis. The CR rate of the whole group was 54% (62% for ALL-treated versus 47% for lymphoma-treated patients; not significantly different), with a median survival for remitters of 28.5 mos. Relapse-free survival of the whole group was 65% at 12 and 25% at 24 mos. Stage IV ALL-treated patients had a median survival of 16.5 versus 10 mos for stage IV lymphoma-treated ones (p = 0.05); the three-years survival was 24 and 10%, respectively. No patients undergoing CNS prophylaxis (ALL-therapy) had neurological complications or late meningeal relapse. The better prognosis of ALL-treated patients, in spite of bone marrow positivity, argues in favor of an ALL-like therapy in all adult lymphoblastic lymphomas, in terms of CR rate, overall survival, and absence of CNS relapse. This therapy must be adopted irrespective of bone marrow findings, and regardless of how localized the lymphoma appears to be.

Clinical utility of terminal deoxynucleotidyl transferase and adenosine deaminase determinations in adult leukemia with a lymphoid phenotype.

A prospective study was done to assess the clinical utility of terminal deoxynucleotidyl transferase (TdT) and adenosine deaminase (ADA) assays in adult leukemia with a lymphoid phenotype. The study population consisted of 58 patients with adult lymphoblastic leukemia (ALL) at onset, 12 with lymphoblastic lymphoma, 15 with acute unclassifiable leukemia (AUL), and 30 with lymphoid or mixed acute phase of Philadelphia chromosome-positive (Ph' +) chronic myelogenous leukemia (CML). TdT was present in all cases of T-ALL, in 90% of non-T, non-B ALL, and absent in B-ALL; the ADA activity was significantly higher (P less than .01) in T-ALL. TdT was found in 75% of lymphoblastic lymphomas, in 78% of lymphoid, and in 50% of mixed CML transformations; higher ADA activity correlated with TdT positivity in AUL and CML blastic transformations (P less than .001). TdT-positive ALL had a better chance of response to therapy than TdT-negative ALL (P less than 0.01), but survival was not statistically different. TdT was undetectable in the peripheral blood of patients with ALL in complete remission and within the normal range in bone marrow (0.1%-8% of nucleated cells); median ADA activity was as in control subjects. Relapsing ALL patients had TdT and ADA enzymatic activities as before therapy; TdT immunofluorescence test (IF) was positive in 69% of bone marrow and in 100% of CNS relapses. Twenty percent of TdT-positive ALL at onset became TdT-negative in bone marrow at relapse. TdT IF test was instrumental in detecting meningeal leukemia but neither TdT nor ADA could be used as indicators of complete remission or impending relapse because TdT-positive cells were present in normal marrows and wide fluctuations of TdT IF values and of ADA activity were observed in remission.

Low-grade malignancy non-Hodgkin's lymphomas: prognostic relevance of their clinicopathologic heterogeneity.

We reviewed 182 consecutive adult patients with low-grade malignancy, non-Hodgkin's lymphomas classified according to the Kiel classification, followed at the Division of Hematology, Policlinico S. Matteo, Pavia, from January 1975 to December 1981, to recognize, in each histopathologic type, important subgroups from the prognostic standpoint. Median follow-up was 36 months. No significant differences were observed in the response rate to conventional therapy (radiotherapy for localized disease, CVP for advanced stages) between the 4 cytologic types. The centrocytic-centroblastic lymphoma with diffuse nodal architecture showed an intermediate-grade malignancy (median survival, 50 months) and underwent cytologic progression to the high-grade malignancy centroblastic type in 10% of the cases. Large-cell centrocytic and polymorphic lymphoplasmacytoid lymphomas had a poor prognosis (median survival less than 30 months) when treated with conventional therapy for favorable histologies, and 6% of the cases transformed into the high-malignancy immunoblastic type. Patients with lymphocytic lymphoma with bulky mediastinum had a median survival of 20 months. The identification of these subgroups with a worse prognosis may have therapeutic implications.

Prognostic significance of terminal transferase and adenosine deaminase in acute and chronic myeloid leukemia.

We have analyzed the distribution and prognostic significance of terminal deoxynucleotidyl transferase (TdT) and adenosine deaminase (ADA) in connection with conventional cytology, cytogenetics, response to therapy, and survival. The study population consisted of 78 patients with AML, 44 patients with Ph1 + CML in chronic phase, and 35 adult patients with Ph1 + CML in blastic phase, among which 5 cases presented as Ph1 + acute leukemia. Nine percent of the AML cases were positive for TdT and were characterized by a high percentage of blast cells in bone marrow, myeloid features by cytochemistry and absence of the Philadelphia chromosome. The median ADA values of the TdT+ AML cases were several times higher than those obtained for the TdT- cases. The survival calculated for the two groups of AML cases subdivided according to ADA levels was significantly longer (p less than 0.025) for the patients with low levels of ADA (less than 250 U/10(8) cells). In chronic phase of CML, TdT was absent and ADA values were increased over normal controls only in cases with early signs of transformation. In blastic phase, 31% of the 35 cases were positive for TdT, and ADA values were significantly higher (p less than 0.001) in TdT+ than TdT- cases. The survival calculated from the onset of transformation was significantly longer for the TdT+ acute phase (10.4 mo) compared to the TdT- patients (4.8 mo; p less than 0.025). Four cases presenting as Ph1 + acute leukemia were TdT+ and had elevated levels of ADA; 3 of them responded to ALL therapy, reverting to a stable phase of CML.

Adult acute lymphoblastic leukemia. Response to therapy according to presenting features in 62 patients.

Sixty-two adult patients with acute lymphoblastic leukemia (ALL) were treated with an induction regimen including vincristine, daunorubicin and prednisone (VDP) followed by CNS prophylaxis. Forty-five patients (72.5%) achieved complete remission (CR). The CR were maintained with daily 6-MP and weekly MTX. Monthly reinduction cycles with vincristine and prednisone (plus daunorubicin every three courses) were also given. Median duration of CR was 10.4 months. Overall survival was 17.4 months. The remission rate and length of CR were studied in relation to the clinical and hematological features present at diagnosis. CR rate was adversely influenced by age only over 40 and by tumoral presentation. The length of remission was negatively influenced by tumoral presentation, CNS involvement, high circulating blast count, L2 and L3 cytology, and T or B immunological phenotype. Multiple regression analysis confirmed the weight of FAB morphology in determining the length of remission. Among L2 adult patients, tumoral presentation appears to be the major unfavourable prognostic factor.

Risk of leukemia in patients treated for Hodgkin's disease.

We reviewed 251 consecutive adult patients with Hodgkin's disease treated at the Division of Hematology, Policlinico S. Matteo, Pavia, from January 1970 to December 1979, to assess the risk of development of acute leukemia. The median time of follow-up was 48 months (range 6-135). No leukemia occurred in 88 patients treated with radiotherapy or chemotherapy alone. Six acute non-lymphoid leukemias occurred in the group of 163 patients treated with MOPP and radiotherapy (crude rate of leukemia of 7.5 per 1000 person-years at risk). All cases were in clinical remission and off therapy; the latent period from initiation of therapy to onset of leukemia ranged between 30 and 90 months. The actuarial probability of leukemia at five and seven years was 2.9 and 4.7% for the entire group of patients, and 3.8 and 5.8% for the combination therapy group. All leukemias , except one, had a preleukemic phase lasting 1-12 months, with cytopenia and dysplastic marrow. The median survival after leukemia was 4.7 months.

Clinical relevance of terminal transferase and adenosine deaminase in leukemia.

Terminal Transferase (TdT), Adenosine Deaminase (ADA), immunological membrane markers, cytochemical reactivity and cytogenetics were analyzed in 226 patients with ALL, AUL and AML, in 70 patients with CML and in 3 cases of Ph' positive acute leukemia presenting as ALL. TdT was tested in peripheral blood and bone marrow with both the biochemical and immunofluorescence (IF) methods, and ADA was determined biochemically only in peripheral blood cells. By using conventional cytochemistry, cell surface markers determinations, TdT and ADA analysis, three distinct groups are recognized in ALL at presentation: T-ALL with TdT+ and very high ADA values; non-T, non-B ALL with TdT+ and intermediate levels of ADA; B-ALL with TdT absence and low levels of ADA. Clinical presentation and responses to therapy in adult and children ALL were correlated to TdT determinations. The median survivals in adults, calculated for TdT+ and TdT- groups, were 14.2 and 5.6 months, respectively. TdT and ADA were determined in ALL during remission. The wide fluctuation observed for TdT IF and ADA values prevented a reliable monitoring of remissions. At relapse, TdT and ADA values were similar to those found for ALL at presentation; TdT IF determinations were diagnostic in cases showing CNS involvement as the only localization. Forty per cent of AUL and 11% of AML cases were positive for TdT; the medians of ADA values of the TdT+ cases in both AML and AUL were several times higher than those obtained in the TdT- group. While TdT positivity and high ADA had a favorable prognostic value in AUL, similar conclusions can not be drawn at the moment for AML. In chronic phase of CML, TdT was strictly negative and ADA values were increased over the control line only in cases showing initial signs of transformation. In acute phase, the cases positive for TdT (32%) presented a significantly higher ADA activity than the TdT negative ones. The actuarial survival curves for the TdT+ and TdT- groups differ significantly, presenting median survivals from onset of phase of 11 and 4.8 months respectively. The three cases of Ph' positive ALL were all TdT+, presented high ADA values and entered chronic phase of CML after therapy.