ABSTRACT
263 patients (median age 65+/-10 years) with multiple myeloma were treated with cyclophosphamide-prednisone. Out of this cohort, 103 patients had progressive disease and were randomly assigned to either VAD (vincristine, doxorubicin, dexamethasone; 50 cases) or VMBCP (vincristine, BCNU, cyclophosphamide, melphalan and prednisone; 53 cases). There were no statistical differences between the two groups with the respect to clinical, biological and radiological parameters. There was no difference in survival between the VAD and VMBCP groups. The 4 months response rate was similar in the two groups (50% VAD, 56% VMBCP). With multivariate analysis for survival (Cox model), two factors had a statistically significant impact: Karnofsky index (> 60) and albuminaemia (< 34 g/l). With both Karnofsky index > 60 and albuminaemia > or = 34 g/l, the median survival was 29 months v 2 months with a Karnofsky index < or = 60 and albuminaemia < 34 g/l (P<0.05). In conclusion, VAD or VMBCP had similar activity for salvage treatment in MM refractory or relapsing to first-line treatment with cyclophosphamide-prednisone.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Multiple Myeloma/drug therapy , Adult , Aged , Aged, 80 and over , Carmustine/administration & dosage , Cyclophosphamide/administration & dosage , Dexamethasone/administration & dosage , Doxorubicin/administration & dosage , Female , Humans , Male , Melphalan/administration & dosage , Middle Aged , Prednisone/administration & dosage , Prognosis , Salvage Therapy , Survival Rate , Treatment Outcome , Vincristine/administration & dosageABSTRACT
There are no well-defined host markers to determine which patients with a diagnosis of monoclonal gammopathy of undetermined significance (MGUS) will progress to multiple myeloma (MM). In this preliminary study we measured plasmatic soluble Fe gamma receptor type III (sFe gamma RIII or sCD16) in 54 individuals with MGUS. 35 patients with multiple myeloma (MM) and 29 healthy controls. We confirmed, through receiver operating characteristic (ROC) curve analysis, that a low level of sCD16 discriminates MM patients from controls. Indeed, for a sCD16 value of 1.3 micrograms/ml, the sensitivity, as well as the specificity, of this discrimination were both equal to 83%, i.e. 83% of MM patients had a plasmatic sCD16 value < 1.3 micrograms/ml compared with only 17% of controls. Moreover, ROC curve analysis showed that a low sCD16 level also identifies among MGUS patients a subgroup of patients who rapidly progress towards multiple myeloma: in this comparison, for a sCD16 level of 1.3 micrograms/ml. sensitivity and specificity were 70% and 79% respectively. Therefore a low sCD16 level in MGUS indicated a high likelihood of rapid evolution of MM. In contrast to sCD16, soluble IL-6R did not appear to be discriminant in this study.
Subject(s)
Multiple Myeloma/diagnosis , Paraproteinemias/diagnosis , Receptors, IgG/blood , Adult , Aged , Aged, 80 and over , Biomarkers , Disease Progression , Enzyme-Linked Immunosorbent Assay , Female , Humans , Interleukin-6/blood , Male , Middle Aged , Prognosis , Sensitivity and SpecificityABSTRACT
The majority of low grade non-Hodgkin's follicular lymphoma undergo clinical progression to intermediate and high grade lymphoma, but the molecular mechanisms involved in this transformation are not yet well understood. In this article, we describe the case of a 66 year old man with follicular non-Hodgkin's lymphoma (NHL), in whom a centroblastic leukaemic transformation led to death in six months, despite a transient period of remission. At the time of transformation, cytogenetic analysis revealed the original coexistence of t(14;18)(q32;q21) and t(8;22)(q24;q11). These results were confirmed by fluorescent in situ hybridization, while molecular analysis showed a BCL2-JH rearrangement but failed to detect a c-myc rearrangement or any additional p53 mutation. Our observations would therefore suggest other mechanisms to be involved in the transformation of follicular NHL.
Subject(s)
Chromosomes, Human , Lymphoma, Follicular/genetics , Transformation, Genetic , Translocation, Genetic , Aged , Chromosomes, Human, Pair 14 , Chromosomes, Human, Pair 18 , Chromosomes, Human, Pair 22 , Chromosomes, Human, Pair 8 , Fatal Outcome , Humans , MaleABSTRACT
We retrospectively analyzed overall survival and survival after progression in 91 patients with low-grade follicular lymphoma (LGFL). Histological subtype was B in 75 patients and C in 16 patients. Twelve patients with localized disease received involved-field radiotherapy; seven patients without bulky disease had no initial therapy. The remaining 72 patients received long-term chlorambucil (9 patients), MOPP or COPBleo (42 patients), or a CHOP-derived regimen (21 patients). Forty-two patients (46%) achieved a complete remission (CR) and 28 patients (31%) achieved a partial remission; 48 of these 70 patients relapsed or progressed. Nineteen of the other 21 patients with stable LGFL progressed. Two other patients failed to respond and rapidly died. Thirty-two of the 67 patients with progressive or relapsed LGFL have died. Median overall survival was 111 months. Age > or = 70 years, male sex, B symptoms, histological subtype follicular mixed-cell NHL, tumor size > or = 10 cm, number of extranodal sites of disease > or = 2, pleural effusion, and Ann Arbor stage III or IV were found to adversely influence overall survival. Failure-free survival < 24 months, failure to achieve a CR after the progression, initial histological subtype follicular mixed cell, initial Ann Arbor stage III or IV, and initial tumoral size > or = 10 cm were found to adversely influence survival after progression. Our results suggest that most prognostic factors for overall survival in LGFL are related to histological subtype or tumor burden. Some initial adverse prognostic factors for survival may be also associated with a poor survival after progression.
Subject(s)
Lymphoma, Follicular/epidemiology , Lymphoma, Non-Hodgkin/epidemiology , Adult , Aged , Aged, 80 and over , Female , Humans , Lymphoma, Follicular/mortality , Lymphoma, Non-Hodgkin/mortality , Male , Middle Aged , Prognosis , Retrospective Studies , Survival RateABSTRACT
A randomized trial has been performed in which 91 patients with stage III myeloma and additional severe criteria were randomly allocated to either VAD or VMBCP. No significant difference was noted between these two groups using the following criteria: response rate (VMBCP: 54%; VAD: 39%), impact on symptoms, median survival (VMBCP: 14 months, VAD: 17 months). However, toxic effects and refusal to pursue treatment were more frequent with VAD than with VMBCP (12 v 6). Therefore, in this trial, VMBCP appears to be more useful than VAD.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Multiple Myeloma/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carmustine/administration & dosage , Cyclophosphamide/administration & dosage , Dexamethasone/administration & dosage , Dexamethasone/adverse effects , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Female , Humans , Male , Melphalan/administration & dosage , Middle Aged , Multiple Myeloma/mortality , Prednisone/administration & dosage , Prognosis , Vincristine/administration & dosage , Vincristine/adverse effectsABSTRACT
100 febrile patients with chemotherapy-induced neutropenia (less than 0.5 x 10(9)/l) were empirically treated by ceftriaxone (2 g daily in adults, 50 mg/kg daily in children, as a once daily injection) and amikacin (15-20 mg/kg daily). The mean age was 41 years (range 8-72). 51 patients had acute leukemia, 29 non-Hodgkin's lymphoma, 12 Hodgkin's disease, 8 other disorders. 23 febrile episodes were bacteriologically documented (gram-positive: 13 patients; gram-negative: 8 patients; Candida: 2 patients) including 13 cases of bacteremia; 10 were clinically documented, and 67 remained of undetermined origin. Apyrexia was obtained in 39 patients by ceftriaxone plus amikacin alone (success), in 36 patients after the addition of vancomycin and/or amphotericin B (improvement), whereas in the remaining 25 patients it was necessary to substitute the study drug. The failure rate was correlated to the duration of neutropenia: 0/13 when neutropenia less than 6 days; 3/41 (7%) when 6-10 days; 22/46 (48%) when greater than 10 days. Only 2/20 (10%) of patients with neutropenia greater than 20 days were treated with ceftriaxone plus amikacin alone. 9 of the 23 bacteriologically documented episodes were successes (including 6 of the 11 cases due to Staphylococcus), 7 were improvements and 7 were failures (including the 3 cases due to Pseudomonas). No side effects were seen. Ceftriaxone plus amikacin is an effective firstline antibiotic combination in the treatment of febrile neutropenic patients.
Subject(s)
Amikacin/therapeutic use , Bacterial Infections/drug therapy , Ceftriaxone/therapeutic use , Neutropenia/complications , Acute Disease , Adolescent , Adult , Aged , Bacterial Infections/etiology , Child , Drug Therapy, Combination/therapeutic use , Humans , Leukemia/complications , Lymphoma, Non-Hodgkin/complications , Middle Aged , Neutropenia/chemically inducedABSTRACT
Over a period of 14 years, we treated 70 cases of acute promyelocytic leukemia (APL) with 3 different chemotherapy protocols. In protocol 1, patients received high dose daunorubicin (DNR) alone for induction, followed by regular reinduction courses and continuous maintenance therapy with 6 mercaptopurine (6 MP) and methotrexate (MTX) during 3 years. In protocol 2, induction with high dose DNR and Ara C was also followed by regular reinduction courses, but without continuous maintenance therapy. Protocol 3 randomized high dose Amsacrine (AMSA) or Rubidazone in association with Ara C, for induction and consolidation, this was followed by reinduction courses and continuous maintenance therapy with 6 MP and MTX. During the induction all patients received, prophylactic heparinization and platelet transfusions. Fifty six patients (80%) achieved complete remission (CR), 13 patients (18.5%) had early death (ED) or hypoplastic death (HD), and 1 patient had true resistant leukemia. Only two patients died of hemorrhage. Median actuarial disease free survival (DFS) was 16.5 months and a plateau at 29.1% was reached after 29 months. Patients with fever at diagnosis had a significantly lower CR rate while age below 20 years and circulating blasts above 0.5 × 10(9)/1 were associated with shorter DFS. The CR rate did not significantly differ between protocols 1, 2 and 3 (87.5%, 80% and 60% respectively) but 9 of the 30 patients on protocols 2 or 3 had ED or HD, compared to 4 of the 40 treated with protocol 1 (p < 0.05). DFS was significantly shorter in protocol 2, which included no continuous maintenance chemotherapy, than in protocols 1 and 3. Median actuarial survival was significantly shorter in patients treated with protocols 2 or 3, compared to protocol 1. These results suggest that high dose DNR alone, associated with adequate prophylaxis of disseminated intravascular coagulation, gives very high CR rates in APL, with short periods of aplasia and limited toxicity. Combinations of an anthracycline or AMSA at the doses used with regular dose Ara C may be too toxic. Although this was not a randomized trial, our findings also suggest a possible benefit of prolonged continuous maintenance therapy with 6 MP and MTX in APL.
ABSTRACT
IgM myeloma is a rare plasma cell neoplasia, with an estimated incidence of 0.5% in patients with myeloma. Approximately, between 2 and 3.3% of IgM monoclonal gammopathy are IgM myeloma. Six unpublished cases of IgM myeloma, association of an IgM monoclonal gammopathy and an exclusive plasma cell neoplasia, are reported. Forty-six other cases have been found in the literature. The initial clinical characteristics of these patients are: sex-ratio of 1.1, mean age of 62 years, fatigue in 95% of the cases, bone pain in 80%, osteolytic lesions in 78%, fever in 13%, hepatomegaly and splenomegaly in 8%, lymphadenopathy in 10%, hemorrhagic diathesis in 35% and neurologic involvement in 18%. Initial biological features are: anemia in 62% of the cases, creatininemia greater than 20 mg/l in 10%, calcemia greater than 120 mg/l in 24%. Mean serum IgM level is 33 g/l, mean medullary plasmocytosis is 52%. 80% of the patients presented with IgM kappa and only 20% with IgM lambda. Proteinuria with light chains are found in 65%. One-year survival is estimated at 82%, 2-year at 62%, 3-year at 46% with a median of 30 months. No prognostic factor is found. IgM myeloma with characteristics of both myeloma and macroglobulinemia appears well individualized among B-cell neoplasia. However, the distinction between Waldenström's macroglobulinemia and IgM myeloma can be difficult in case of lympho-plasmocytic bone marrow proliferation with osteolytic lesions.
Subject(s)
Immunoglobulin M/immunology , Multiple Myeloma/immunology , Aged , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Multiple Myeloma/diagnosis , Prognosis , Time Factors , Waldenstrom Macroglobulinemia/diagnosis , Waldenstrom Macroglobulinemia/immunologyABSTRACT
We report 11 children (aged less than 20 years) with acute promyelocytic leukemia (APL), who represented 14% of our total number of patients with APL. There were 8 girls and 3 boys and the median age was 13.5 (range 3-19). Extramedullary leukemia was present in only 1 patient and hyperleukocytosis in 3 patients. Cytologically, 9 patients had "classical" APL, and 2 had the microgranular variant APL. Translocation (15;17) was present in all 4 karyotyped patients. Disseminated intravascular coagulation was seen in 8 patients at diagnosis, and was triggered by chemotherapy in 2 other cases. Induction chemotherapy was daunorubicin (DNR) alone in 6 patients, DNR + Ara C in 4 and zorubicin + Ara C in the remaining case. All patients received heparin during induction. Seven patients (64%) achieved complete remission (CR), 2 had resistant leukemia and 2 died during induction. Among the complete remitters, one received no further therapy and relapsed after 4 months, and another died of an unrelated cause after 4 weeks, while still in CR. The 5 others all relapsed after 3 to 13 months. Median survival was 5.5 months. Disease free survival (DFS) was significantly shorter than in our adult APL patients treated with the same regimens. APL is a rare disease in children and our results suggest that it may be associated with short remissions, especially when compared with adult APL. This could justify therapeutic reinforcement in these cases, such as allogeneic bone marrow transplantation, whenever possible, after CR has been achieved.
ABSTRACT
Twenty-nine adult patients with primary myelodysplastic syndromes (MDS) and an excess of marrow blasts were treated by aggressive chemotherapy while still in MDS phase (20 cases) or after progression to ANLL (9 cases). Median age was 47.5 (range 18-68). Twenty-eight patients received a combination of Rubidazone and Ara C and 1 received High dose Ara C. Fourteen patients (48%) achieved complete remission (CR), 5 (17%) were treatment failures (F) and 10 (35%) died during therapy induced aplasia (DA). Median disease free survival was 8.5 months. Median survival of the whole population was 6 months from the onset of treatment, and 17 months in patients achieving CR. These results were significantly less favorable than those obtained at our institution in de novo ANLL with the same chemotherapy regimens. No statistically significant prognostic factors of treatment outcome emerged but patients with normal cytogenetic findings seemed to have both a higher CR rate and longer remissions than patients with abnormal karyotypes. Patients under 50 did not have higher CR rates than older patients, although they had longer remissions (with 3 out of 6 CRs exceeding 2 years). Finally, treatment outcome and survival were identical in patients treated in the MDS phase and in those treated after progression to ANLL. Combination chemotherapy is a highly toxic approach in MDS and essentially seems to benefit younger patients with a normal karyotype, in whom some long remissions can be obtained.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Myelodysplastic Syndromes/drug therapy , Adolescent , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Drug Evaluation , Female , Humans , Leukemia, Myeloid, Acute/drug therapy , Male , Middle Aged , Remission InductionABSTRACT
Childhood acute lymphocytic leukemia (ALL) with partial deletion of the short arm of chromosome 9 (9p-), particularly in the p21-22 region, associated with bulky disease, has been regarded as a possible subgroup of ALL. We have reviewed clinical and cytologic data in 128 cases of ALL (childhood and adult). Four of them had 9p anomalies. Two patients had a deletion in the 9p21 region associated with another deletion (9p13----pter) in one case and with t(1;19)(q21;p13) in the second patient. A third patient had a t(9;14)(p21;q12) balanced translocation associated with 14q22----qter deletion; the last patient showed a t(5;9)(p14;q21) unbalanced translocation also associated with 14q deletion. All four patients had lymphomatous ALL, but immunophenotype was non-T, in the four cases, (non-T, non-B in two patients and common ALL in the two remaining cases). Acute lymphocytic leukemia with 9p anomalies appears relatively frequently and is usually associated with poor prognostic features (i.e., bulk disease and high leukocyte counts) but does not seem restricted to childhood and T-cell lineage.
Subject(s)
Chromosome Deletion , Chromosomes, Human, Pair 9 , Genetic Markers , Leukemia, Lymphoid/genetics , Adolescent , Adult , Child , Chromosome Banding , Female , Humans , Karyotyping , Leukemia, Lymphoid/mortality , Male , PrognosisABSTRACT
Two male patients, aged 36 and 73 years respectively, gradually developed febrile pancytopenia with profound alteration of their general condition and major inflammatory repercussions. No superficial or deep lymph node enlargement was found initially. Patient n degree 2 had an enlarged spleen. In both cases histological examination of the bone marrow showed an extensive and apparently nonspecific myelofibrosis. The subsequent development of superficial lymphadenopathy provided a firm diagnosis of Hodgkin's disease with mixed cellularity. These two cases belong to the category of exceptional massive medullary forms of Hodgkin's disease described by Duhamel et al. in 1979.
Subject(s)
Hodgkin Disease/complications , Primary Myelofibrosis/etiology , Adult , Aged , Female , Humans , Male , Primary Myelofibrosis/diagnosisABSTRACT
This retrospective study concerns 13 patients in whom Hodgkin's disease was diagnosed during pregnancy or immediately after delivery (group I) and 12 patients with Hodgkin's disease who had one or several pregnancies while under treatment (group II). In group I, Hodgkin's disease was diagnosed in early pregnancy in 4 patients who all had therapeutic abortion: 3 remain in prolonged complete remission and 1 had a late relapse; 9 cases were diagnosed in late pregnancy or after delivery: 3 were treatment failures, 2 had a relapse and 4 remain in complete remission. In group II patients, 3 pregnancies occurred during initial chemotherapy and were interrupted; 5 pregnancies occurred during subsequent radiotherapy or (for earlier patients) maintenance chemotherapy, and 4 of them were interrupted; 9 pregnancies occurred within 2 years of completing treatment, and 7 after 2 years. Of the 12 patients in group II, only 2 had a relapse whereas 10 remain in complete remission. Although they should be interpreted with caution, these data suggest that Hodgkin's disease diagnosed in late pregnancy or after delivery might be more active, and they justify therapeutic abortion when diagnosis is made in early pregnancy. They do not indicate a high risk of relapse in treated Hodgkin's disease patients during a subsequent pregnancy, even if it occurs shortly after treatment.
Subject(s)
Hodgkin Disease/diagnosis , Pregnancy Complications, Neoplastic/diagnosis , Abortion, Therapeutic , Adolescent , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Female , Fertility , Hodgkin Disease/pathology , Hodgkin Disease/therapy , Humans , Neoplasm Staging , Postpartum Period , Pregnancy , Pregnancy Complications, Neoplastic/pathology , Pregnancy Complications, Neoplastic/therapy , Retrospective Studies , Time FactorsSubject(s)
Pipobroman/therapeutic use , Thrombocythemia, Essential/drug therapy , Adult , Female , HumansABSTRACT
16 adult idiopathic thrombocytopenic purpura (ITP) patients, with mean age 51 years, were treated by 5 weekly slow intravenous infusions of vinblastine (0.1 mg/kg). When a complete or partial response (CR or PR) was obtained, slow infusions were repeated at 2-weekly then monthly intervals, as maintenance therapy. In 4 cases with ITP of recent onset, but presenting contraindication or failure to prednisone and high dose intravenous immunoglobulins, CR was obtained in all patients after 4 to 15 days (mean 9.5). Only one of these patients relapsed. In 12 cases of refractory chronic ITP (of whom 10 had been splenectomized), there were 2 CR, 6 PR and 4 failures. The 8 responding patients had a mean interval to response of 20 days. The 6 PR were short and did not exceed 15 days. Our results do not support a superiority of this treatment compared to other modes of administration of vinca alkaloids in ITP (intravenous bolus, vinca loaded platelets).
Subject(s)
Purpura, Thrombocytopenic/drug therapy , Vinblastine/therapeutic use , Adult , Aged , Female , Humans , Infusions, Intravenous , Male , Middle Aged , Platelet Count , Purpura, Thrombocytopenic/blood , Vinblastine/adverse effectsABSTRACT
We report 60 cases of chronic and subacute myelomonocytic leukaemias (CMML and SMML) in the adult, using the FAB group criteria. The M/F sex ratio was 3.3 and the mean age 67.5 years. Splenomegaly was found in 32% of cases, hyperleucocytosis in 52% of cases and mean blood monocytosis was 4.3 X 10(9)/l. Marrow smears showed an excess of blasts in 57% of patients, a moderate increase in monocytes in most cases and frequent myelodysplastic features. An increase in serum lysozyme and polyclonal hypergammaglobulinaemia were usual and clonal cytogenetic anomalies found in about half of the patients tested. Treatment was usually palliative and the median survival was 28 months, a blastic transformation being responsible for a third of the deaths. Prognostic factors at diagnosis were analysed retrospectively in the 46 patients who had sufficient follow up. Percentage of marrow blasts haemoglobin level and blood monocytosis at diagnosis, were subject to multivariate analysis, resulting in a discriminant 'score'. This allowed assignment of each patient into one of two prognostic subgroups (10.9% probability of error): a poor prognosis one, with a life expectancy of less than 1 year and a high risk of acute transformation (subgroup termed SMML) and a better prognosis subgroup (termed CMML), with some CMML patients surviving over 5 years.
Subject(s)
Leukemia, Myeloid/pathology , Adult , Aged , Aged, 80 and over , Chromosome Aberrations , Female , Humans , Leukemia, Myeloid/blood , Leukemia, Myeloid/mortality , Male , Middle Aged , Prognosis , Retrospective StudiesABSTRACT
A male patient, aged 23 years, with no notable previous history, was admitted to hospital because of fever, splenomegaly, and pancytopenia. The bone marrow was infiltrated by mature looking histiocytes displaying erythrophagocytosis. Other findings included polyclonal hypergammaglobulinemia, elevated transaminases, hypofibrinogenemia, and hypertriglyceridemia. A diagnosis of virus-associated hemophagocytic syndrome was made and virology studies attributed it to herpes simplex virus type 1. Therapy with acyclovir, high dose i.v. immunoglobulins, and vinblastine was unsuccessful. With the addition of prednisone, a remission, with disappearance of histiocytic marrow involvement, was obtained but was of short duration, and the outcome was fatal.
Subject(s)
Erythrocytes , Herpes Simplex/complications , Histiocytic Sarcoma/etiology , Phagocytosis , Adult , Bone Marrow/pathology , Histiocytes/pathology , Histiocytic Sarcoma/pathology , Histiocytic Sarcoma/therapy , Humans , MaleABSTRACT
A total of 17 patients, 6 female and 11 male (age range 13 to 56 years), received high dose Ara-C for treatment of refractory acute myelogenous leukemia. Ara-C was given at 3 g/m2 twice daily for 6 days as a 1 infusion. 1 patient (with induced acute leukemia) was treated directly, two after failure of a chemotherapy schedule containing the usual dose Ara-C, 12 for first relapse and 2 for subsequent relapse. Maximum follow up is 16 months. Beside hematological toxicity, systemic tolerance was good with no neurological of cutaneous effects. Despite preventive corticoid eyewash, ocular complications occurred in 6 cases, mild and resolvable in 5 of them. The immediate results were as follows: 3 deaths during induction (18%); 6 failures (35%); 8 complete remissions (CR) (47%). After primary chemo-resistance (two cases) failure was always noted. In 3 cases, after less than 12 infusions had been given, 2 failures and 1 very short CR were noted. In 2 patients, when doxorubicin was added to Ara-C, we observed 1 death during induction and 1 failure. Of the patients achieving CR 8 were treated by periodic courses with high dose Ara-C and 4 of them relapsed. The longest failure free duration was 11 months. Median survival duration of the 17 patients is 5 months.