C. Rozman

Bone Marrow Transplantation for Chronic Myelogenous Leukemia in Chronic Phase: Increased Risk for Relapse Associated with T-Cell Depletion

Data on 405 patients with chronic myelogenous leukemia who received bone marrow transplants in chronic phase were analyzed for factors predictive of outcome. The 4-year actuarial probability of relapse was 19% (95% confidence interval [CI], 12% to 28%) and of survival, 55%. In multivariate analyses the probability of relapse was higher for recipients of T-cell-depleted bone marrow compared with recipients of non-T-cell-depleted bone marrow (relative risk, 5.4; P less than 0.0001) and for patients who did not develop chronic graft-versus-host disease (95% CI, 50% to 60%) with patients who did (relative risk, 3.1; P less than 0.01). The probability of survival was lower for patients who developed moderate to severe acute graft-versus-host disease than for patients with no or mild acute graft-versus-host disease (relative risk, 3.7; P less than 0.0001), and in patients aged 20 or older than in younger patients (relative risk, 2.6; P less than 0.0002). Duration of disease before transplant was not associated with outcome. Bone marrow transplantation done in the chronic phase of chronic myelogenous leukemia offers some patients prolonged leukemia-free survival. The T-cell-depleted grafts are associated with an increased probability of relapse.

Chemotherapy compared with bone marrow transplantation for adults with acute lymphoblastic leukemia in first remission.

OBJECTIVEnTo compare efficacy of intensive postremission chemotherapy with allogeneic bone marrow transplantation in adults with acute lymphoblastic leukemia (ALL) in first remission.nnnDESIGNnRetrospective comparison of two cohorts of patients.nnnSETTINGnChemotherapy recipients were treated in 44 hospitals in West Germany in two cooperative group trials; transplants were done in 98 hospitals worldwide.nnnPATIENTSnPatients (484) receiving intensive postremission chemotherapy and 251 recipients of HLA-identical sibling bone marrow transplants for ALL in first remission. Patients ranged from 15 to 45 years of age and were treated between 1980 and 1987.nnnMAIN RESULTSnSimilar prognostic factors predicted treatment failure (non-T-cell phenotype, high leukocyte count at diagnosis, and 8 or more weeks to achieve first remission) of both therapies. After statistical adjustments were made for differences in disease characteristics and time-to-treatment, survival was similar in the chemotherapy and transplant cohorts: Five-year leukemia-free survival probability was 38% (95% CI, 33% to 43%) with chemotherapy and 44% (CI, 37% to 52%) with transplant. No specific prognostic group had a significantly better outcome with one treatment compared with the other (6% for the difference; CI, -3% to 15%). Causes of treatment failure differed: With chemotherapy, 268 (96%) failures were from relapse and 11 (4%) were treatment-related; with transplants, 43 (32%) failures were from relapse and 92 (68%) were treatment-related.nnnCONCLUSIONSnThese results suggest that bone marrow transplants currently offer no special advantage over chemotherapy for adults with acute lymphoblastic leukemia in first remission.

Patients with multiple myeloma requiring long-term dialysis: presenting features, response to therapy, and outcome in a series of 20 cases

Summary. From January 1982 to December 1993, 30 patients with multiple myeloma (MM) required haemodialysis (HD) at our institution. The subgroup of 20 patients who survived more than 2 months on HD is the subject of this study. Four patients were already on HD, due to previous nephropathy, when MM was diagnosed. 13 patients presented with acute renal failure and were on dialysis from the time of diagnosis. The remaining three cases developed renal failure later in the course of the disease. The objective response rate was 40% (8/20). Only two patients could discontinue HD (one had a late partial recovery and one received a kidney graft). Mean hospitalization per year was 19.3 d. The subgroup of patients who survived < 1 year spent a mean of 38.3 d in hospital. Whereas in the subgroup with a survival > 1 year mean hospitalization days was 9.6 (P < 0.001). The median survival was 20 months and six patients survived for > 3 years. In summary, patients with MM and severe renal failure who survive the first 2 months on dialysis have an objective response rate to chemotherapy of 40% and a median survival of almost 2 years, with 30% long‐term survivors.

Survival of multiple myeloma patients who are potential candidates for early high-dose therapy intensification/ autotransplantation and who were conventionally treated.

PURPOSEnTo analyze the outcome of patients with multiple myeloma (MM) who were potential candidates for early high-dose therapy (HDT) intensification followed by autotransplantation from a series treated with conventional chemotherapy.nnnPATIENTS AND METHODSnFrom January 1985 through December 1989, 487 patients with symptomatic MM were entered onto a randomized study to compare melphalan and prednisone (MP) versus vincristine, cyclophosphamide, melphalan, and prednisone (VCMP) /vincristine, carmustine (BCNU), doxorubicin, and prednisone (VBAP). The sub-group of 77 patients who could have been candidates for early intensification with HDT followed by stem-cell support (ie, < 65 years of age, stage II or III disease, performance status < 3, and objective or partial response to initial chemotherapy) are the subjects of this report.nnnRESULTSnSeventy-seven of 487 patients could have been candidates for early intensification. The median age was 56 years (range, 27 to 64). At diagnosis, 12% had abnormal renal function, 16% hypercalcemia, and 42% serum beta 2-microglobulin level > or = 6 mg/L; 62% had stage III disease at diagnosis. Thirty-six patients were initially treated with MP and 41 with VCMP/VBAP. The median response duration to initial chemotherapy was 22 months, and the actuarial probability of being in continued first response at 5 years was 14%. After a median follow-up time of 58 months, 59 patients have died, one was lost to follow-up evaluation, and 17 are still alive 69 to 119 months after initial chemotherapy. The median survival time from initiation of treatment was 60 months and from the time when autotransplantation would be considered, 52 months. The only independent prognostic parameter for survival was renal function at diagnosis.nnnCONCLUSIONnThe median survival time of patients with MM who are less than 65 years of age and who respond to initial chemotherapy is 5 years. This survival duration is similar to that reported in selected series of patients given early HDT and stresses the importance of ongoing randomized trials to determine the role of HDT in the treatment of younger myeloma patients.

Prognostic Significance of Bone‐Marrow Patterns in Chronic Lymphocytic Leukaemia

Summary. Bone‐marrow biopsy has been performed in 63 cases of chronic lymphocytic leukaemia (CLL). Four different histological patterns were observed: (a) interstitial (lymphoid infiltration without displacement of fat cells) in 12 cases; (b) nodular (abnormal lymphoid nodules without interstitial infiltration) in 10 cases; (c) mixed (combination of the first two patterns) in 21 cases; and (d) diffuse (replacement of both haemopoietic and fat cells by lymphoid infiltration) in 20 cases.

Risk factors for interstitial pneumonia following bone marrow transplantation for severe aplastic anaemia

Summary. Data from 547 patients with aplastic anaemia who received bone marrow transplants from HLA‐identical siblings were analysed to determine factors associated with the risk of interstitial pneumonia (IPn). IPn developed in 92 patients (17%). 37% of cases were associated with cytomegalovirus infection and 22% with other organisms: in 41% of cases no organism was identified. The case fatality rate was 64%; the mortality rate due to IPn was 11%. In multivariate analysis, four factors were associated with an increased probability of interstitial pneumonia: use of methotrexate rather than cyclosporine after transplantation (relative risk, 2.8: P<0.0008); occurrence of moderate to severe acute graft‐versus‐host disease (relative risk, 2.2; P<0.002); inclusion of total body radiation in the pretransplant preparative regimen (relative risk 2.2, P<0.004); and patient age >20 (relative risk 1.7, P<0.002). The probability of IPn ranged from 4% for patients with none of these adverse risk factors to 51% (relative risk of 13.4) for patients with all four. The incidence of IPn decreased significantly between 1978 and 1985, paralleling a decrease in the use of total body radiation pretransplant for immune suppression and methotrexate post‐transplant for prophylaxis against graft‐versushost disease.

Chronic lymphocytic leukemia: a changing natural history?

There are some data suggesting that the natural history of chronic lymphocytic leukemia (CLL) may be changing, but a systematic analysis of this topic is lacking. To address this issue, we examined two cohorts of CLL patients in whom the diagnosis was established in 1960–1979 (group I) and in 1980–1989 (group II), respectively. Striking differences were observed between both cohorts. The diagnosis in the second group was established at higher age (65.8 vs 61.3 years; Pu2009=u20090.0001), both in males (63.8 vs 59.1 years; Pu2009=u20090.004) and females (68.3 vs 64.2 years; Pu2009=u20090.01); the proportion of patients in whom the diagnosis was established in low-risk clinical stage (Binet’s A) was significantly higher in group II (65.7% vs 42.6%; P <0.001), and the survival was more than double in group II (median of 11.1 vs 5.3 years; P < 0.0001). moreover, the impact of the disease on life expectancy was much lower in the more recent cohort. these differences may be due, at least in part, to changes in the natural history of the disease.

Hodgkin's disease presenting as a cholestatic febrile illness: incidence and main characteristics in a series of 421 patients

Abstractu2002In order to determine the frequency and characteristics of patients with liver abnormalities as the presenting manifestation of Hodgkins disease (HD), 421 consecutive HD patients were studied. Six patients in the series (1.4%) presented with liver abnormalities that led to of a liver biopsy and the subsequent diagnosis of HD. All had fever prior to HD diagnosis, four frank jaundice, and one hepatic failure. No patient had pruritus. Moderate hepatomegaly was present in four patients. Cholestasis was observed in all cases; in most patients a moderate increase in the transaminase activity was also seen. Two patients had a mild rise in the serum LDH, four had leukopenia, and one eosinophilia. At liver histologic study, Reed-Sternberg cells were demonstrated in four patients; in the remaining two, the presence of atypical histiocytes, lymphocytes, and eosinophils was highly suggestive of HD, the latter diagnosis being confirmed by subsequent study of bone marrow and/or retroperitoneal lymphadenopathies. In three of the six patients, HD was not demonstrated in sites other than the liver. Three patients older than 60 years died shortly after HD diagnosis. By contrast, three patients younger than 40 years showed a dramatic response to chemotherapy: two of them had a further relapse, and one is considered cured after 14 years of continuous remission. Liver disease constitutes an infrequent form of HD presentation which must be included in the differential diagnosis of any patient with fever of unknown origin.

Prolymphocyte Leukaemia of T‐Cell Type: Immunological, Enzymatic and Ultrastructural Morphometric Characteristics

Summary. A case of prolymphocytic leukaemia with immunological characteristics of T‐cell type is reported. Three noteworthy findings can be emphasized: the presence of C3 receptors on the T‐prolymphocytes, the study of the acid‐phospha‐tase isoenzymatic pattern, which showed an increased band 3 with absence of band 3b, and the morphometric ultrastructural investigation. Cytochemistry and ultra‐structural morphometry may be useful for a more precise characterization of prolymphocytic leukaemia and help to distinguish it from other lymphoprolifera‐tive disorders.

Maintenance treatment with interferon alpha-2b in multiple myeloma: a prospective randomized study from PETHEMA (Program for the Study and Treatment of Hematological Malignancies, Spanish Society of Hematology)

The objectives of the present study were to investigate whether interferon alpha (IFN) maintenance could prolong response duration and survival in patients with multiple myeloma (MM) in objective response and to analyze the characteristics of relapse and subsequent survival. From January 1991 to November 1994, 92 patients from the Spanish Cooperative Group PETHEMA with MM in objective response after 12 courses of VCMP/VBAP chemotherapy were randomized to receive IFN maintenance vs no treatment until relapse. Prognostic factors at diagnosis were similar in both groups. IFN was administered at a starting dose of 3u2009mU/m2 three times per week. The IFN toxicity was moderate with granulocytopenia and fatigue being the most common adverse effects. Median duration of response from randomization until relapse was 13 months in the IFN group vs 7.7 months in the no treatment arm (Pu2009=u20090.042). Median survival from randomization was 38.8 months for patients given IFN vs 32.7 months for those allocated to the no treatment arm (Pu2009=u20090.12). Features at relapse were similar in patients who received IFN maintenance and in those assigned to no treatment. Finally, survival from relapse was identical in both groups. In summary, our results show a significant prolongation of response in patients maintained with IFN with no significant influence on survival. In addition, in our series features at relapse and subsequent outcome were similar in both groups.