Bone marrow monosomy 7: hematologic and clinical manifestations in childhood and adolescence

The hematologic manifestations and clinical course are described for six children and adolescents with bone marrow monosomy 7. One child with secondary acute myelogenous leukemia had monosomy 7 plus a marker chromosome; the remaining patients had marrow monosomy 7 as the only karyotypic abnormality. The hematologic abnormalities were diverse, but the majority of patients had a smoldering preleukemic or myeloproliferative phase. Leukemic blasts were either undifferentiated or demonstrated evidence of myeloid differentiation. All patients responded poorly to antileukemic therapy. Bone marrow monosomy 7 was observed in one patient with severe marrow hypoplasia. Antileukemic therapy in another patient with greater than 30 per cent marrow blasts was associated with the development of a bone marrow myeloproliferative disorder with persistence of the monosomy 7 karyotype. We speculate that monosomy 7 may be a specific marker for a pluripotent hematopoietic stem cell abnormality that is associated with either blastic leukemia or a myeloproliferative disorder.     

Etoposide in combination with intermediate dose cytosine arabinoside (ID ARA C) given with the intention of further myeloablative therapy for the treatment of refractory or recurrent hematological malignancy.

Thirty-four patients with refractory or recurrent high grade non-Hodgkin's lymphoma (NHL) or acute leukemia were treated with a combination of etoposide, 100 mg/m2 daily, and ara C, 1 g/m2 twice daily, for 5 days (VPARAC). This therapy was given in the anticipation that remissions thus achieved would be 'consolidated' with myeloablative therapy supported by bone marrow transplantation (BMT). The complete remission rate (CR) in patients with NHL was 3/18 (17 per cent) with partial responses (PR) seen in a further four patients, giving an overall response rate of 39 per cent. Four patients (three in CR, one in PR) proceeded to the planned consolidation treatment. Complete remission was achieved in 2/8 (25 per cent) patients with acute myelogenous leukemia (AML) and in 2/8 patients with acute lymphoblastic leukemia (ALL). Three of these patients subsequently had myeloablative consolidation therapy with BMT. There were four treatment-related deaths (NHL, two; AML, one; ALL, one). In poor risk patients with high grade NHL and acute leukemia, VPARAC is an effective remission induction programme in 21 per cent of patients. Seven of the original 34 patients received the intended 'curative' therapy, of whom only four are alive and well 1 year later.     

Ifosfamide and mitoxantrone (I-M) in relapsed and refractory high grade non-Hodgkin's lymphoma and Hodgkin's disease

Fifty-five patients, initially diagnosed as having advanced high grade non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) refractory to first-line treatment or in relapse, were treated with ifosfamide 6 g/m2, infused over 48 h, followed by mitoxantrone 12 mg/m2. The regimen repeated at three-weekly intervals. Of 32 patients with NHL evaluable for response, 10 (31 per cent) achieved complete remission and five partial remission, giving an overall response rate of 47 per cent. Two patients subsequently went on to bone marrow transplant (BMT)--one allogeneic and the other autologous. Of 17 patients with HD evaluable for response, six (35 per cent) achieved complete remission and six partial remission, giving an overall response rate of 71 per cent. Two of this group also went on to BMT (both autografts). The principal toxicity was neutropenia, though central nervous system changes were observed in 10 patients. Given the need to offer alternative treatment of patients in these categories, this combination (I-M) is clearly of value in relapsed patients especially where therapeutic options are limited because of previous multi-drug treatment.     

Therapy-related myelodysplasia and secondary acute myelogenous leukemia after high-dose therapy with autologous hematopoietic progenitor-cell support for lymphoid malignancies.

PURPOSE: To evaluate the incidence of and risk factors for therapy-related myelodysplasia (tMDS) and secondary acute myelogenous leukemia (sAML), after high-dose therapy (HDT) with autologous bone marrow or peripheral-blood progenitor-cell support, in patients with non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Between January 1985 and November 1996, 230 patients underwent HDT comprising cyclophosphamide therapy and total-body irradiation, with autologous hematopoietic progenitor-cell support, as consolidation of remission. With a median follow-up of 6 years, 27 (12%) developed tMDS or sAML. RESULTS: Median time to development of tMDS or sAML was 4.4 years (range, 11 months to 8.8 years) after HDT. Karyotyping (performed in 24 cases) at diagnosis of tMDS or sAML revealed complex karyotypes in 18 patients. Seventeen patients had monosomy 5/5q-, 15 had -7/7q-, seven had -18/18q-, seven had -13/13q-, and four had -20/20q-. Twenty-one patients died from complications of tMDS or sAML or treatment for tMDS or sAML, at a median of 10 months (range, 0 to 26 months). Sixteen died without evidence of recurrent lymphoma. Six patients were alive at a median follow-up of 6 months (range, 2 to 22 months) after diagnosis of tMDS or sAML. On multivariate analysis, prior fludarabine therapy (P =.009) and older age (P =.02) were associated with the development of tMDS or sAML. Increased interval from diagnosis to HDT and bone marrow involvement at diagnosis were of borderline significance (P =.05 and.07, respectively). CONCLUSION: tMDS and sAML are serious complications of HDT for NHL and are associated with very poor prognosis. Alternative strategies for reducing their incidence and for treatment are needed.     

Twin-track studies of ifosfamide and mitoxantrone (I-M) in recurrent high grade non-Hodgkin's lymphoma and Hodgkin's disease. Yorkshire Regional Lymphoma and Central Lymphoma Groups.

Fifty-seven patients, initially diagnosed as having advanced high grade non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) refractory to first-line treatment or in relapse, were treated with ifosfamide 6 g/m2, infused over 48 h, followed by mitoxantrone 12 mg/m2. The regimen repeated at three-weekly intervals. Of 33 patients with NHL evaluable for response, 10 (30 per cent) achieved complete remission and six partial remission, giving an overall response rate of 48 per cent. Two patients subsequently went on to bone marrow transplant (BMT)--one allogeneic and the other autologous. Of 18 patients with HD evaluable for response, seven (39 per cent) achieved complete remission and six partial remission, giving an overall response rate of 72 per cent. Two of this group also went on to BMT (both autografts). The principal toxicity was neutropenia, though central nervous system changes were observed in 10 patients. The possibility of increasing the safety of the regimen by increasing the time of infusion to 72 h is discussed. Given the need to offer alternative treatment to patients in these categories, this combination (I-M) is of value in relapsed patients, especially where options are limited because of previous multi-drug treatment. Remissions may not be prolonged but allow the effective application of additional intensive treatment including bone marrow transplantation.     

Extramedullary relapse despite graft-versus-leukemia effect after bone marrow transplantation in a girl with juvenile myelomonocytic leukemia.

A 12 year-old girl with juvenile myelomonocytic leukemia (JMML) and monosomy 7 underwent allogeneic bone marrow transplantation (BMT) from her HLA-matched brother. To monitor the engraftment and the course of the disease we used fluorescence in situ hybridization (FISH) with probes specific for the centromeres of chromosomes X, Y and 7. Complete hematological remission was achieved and confirmed by the virtually exclusive presence of normal male cells in the bone marrow (BM). Acute graft-versus host disease (GvHD) was treated with prednisone and cyclosporine A (CSA) and female cells with monosomy 7 reoccurred in the peripheral blood (PB) and BM. After discontinuation of the immunosuppressive therapy, the leukemic cells with monosomy 7 disappeared again from these compartments. One year after transplantation, isolated extramedullary relapses occurred in lymph nodes and skin, followed by dissemination of blast cells into the BM, whereas the PB cells remained of donor origin. The fact that the leukemic cells fluctuated with the intensity of the immunosuppressive treatment provides evidence of a graft versus leukemia (GvL) effect in this unusually old girl with JMML with a unique extramedullary disease progression.     

Preliminary clinical trial of autologous bone marrow transplantation after in vitro monoclonal antibody and complement treatments in null cell-type acute lymphocytic leukemia

Autologous bone marrow transplantation (BMT) in null cell-type acute lymphocytic leukemia (Null-ALL) was carried out after depletion of leukemia cells from transplanted bone marrow. Patients' autologous bone marrow cells were harvested during remission and treated in vitro with complement and three monoclonal antibodies (NL-1, NL-22 and HL-47) reactive to Null-ALL cells, and then cryopreserved. Three patients were transplanted with the antibody-treated bone marrow cells during the first remission period after preconditioning with intensive chemotherapy and total body irradiation, while transplantations in two other patients, who were in poor clinical condition, were done during the fourth remission period and the third relapse, respectively. Good preservation of hematopoietic stem cells after antibody treatment and cryopreservation of bone marrow cells was demonstrated in all five cases studied. Clinically, prompt recovery of white blood cells and platelets was observed in the three patients who received BMT during the first remission period; two of them have continued remission (2 and 15 months), while the other relapsed after 7 months of remission. these results suggested that autologous BMT with these three antibodies may be an effective mode of therapy for Null-ALL patients.     

Acute leukemia

Recent progress in the treatment of acute leukemia is so rapid and wide-ranged that it is difficult to detail the progress. Therefore we limit this paper focusing following items: 1) FAB classification and therapeutic response; 2) 5000 leukocyte differential and survival; 3) bone marrow transplantation; and 4) over all survival and 5-year survival. 1) FAB classification and therapeutic response: 59 cases of acute non-lymphocytic leukemia were classified according to FAB classification: (M5-16 cases. The differences in the complete remission rate, duration of remission and median survival were not significant among these groups. 2) 5000 leukocyte differential and survival: 86 cases with acute leukemia which achieved complete remission were divided into three groups according to the levels of remaining leukemic cells by 5000 leukocyte differential: 0-1/5000-39 cases, 2-4/5000-24 cases and 5-/5000-23 cases. A close correlation between the leukemic cell level during remission and survival of patients was observed. A marked tendency of longer survival was observed in cases in which leukemic cells decreased during remission and vice versa. 3) Bone marrow transplantation (BMT) therapy: Up to now, 15 patients have been treated and 4 of them are alive now. The longest survival is a case of a 9 year old boy with ALL, who is doing well after BMT for one year and a half. 4) Median survival and 5-year survival: Overall median survival of acute leukemia patients was 7 months (1970-1974) and 12 months (1975-1979). We have experienced 12 patients of 5-year survivors. Out of them, 7 patients are still in remission for more than 6 years. The 5-year survival rate was 0.5% before 1969, and 8.3% after 1970. This indicates a remarkable improvement in the treatment of acute leukemia.     

Autologous Bone Marrow Transplantation in Acute Lymphoblastic Leukemia following In Vitro Treatment with Monoclonal Antibodies and with Complement: Analyses for Two Cases of Failure

Two children with acute lymphoblastic leukemia (ALL) receivedautologous bone marrow transplantation (BMT) using remissionbone marrow treated in vitro with the monoclonal antibodies,CD24 (BA-1), CD9 (BA-2) and CD 10 (BA-3), and with rabbit complement. In one child with second remission ALL, hematopoietic recoveryafter BMT was prompt but, 81 days after BMT, isolated centralnervous system (CNS) relapse occurred. Bone marrow relapse developedthree months later, and she died 11 months after BMT. In patientswith CNS leukemia prior to BMT, as in the present case, moreintensive pretransplant CNS treatment and/or a conditioningregimen may reduce the risk of relapse. In the other patient, with primary refractory ALL in first remission,marrow reconstitution was slower. The patient developed interstitialpneumonitis with pleural effusion, and died 54 days after BMT.No infectious causes could be detected by culture or from serologicalstudies of the pleural effusion. The rationale for applying autologous BMT to children with secondremission ALL and first remission refractory ALL is discussed.     

Allogeneic bone marrow transplantation as therapy for primary induction failure for patients with acute leukemia

The survival of patients with acute leukemia who do not achieve a remission with primary therapy is very poor. High-dose chemoradiotherapy followed by allogeneic bone marrow transplantation (BMT) has been shown to be effective therapy for patients with acute and chronic leukemia. Therefore, we determined the long-term disease-free survival of patients who did not achieve a remission and were then treated with high-dose therapy and bone marrow allografting from matched sibling donors. Twenty-one patients (median age, 28 years) who did not achieve a remission with induction chemotherapy were subsequently treated with allogeneic BMT. After BMT, 90% achieved a complete remission. Six died of complications of the therapy, and six patients relapsed between 27 and 448 days after BMT. Nine patients (43%; median age, 25 years) are alive between 556 and 4,174 days after BMT. The cumulative probability of disease-free survival at 10 years is 43%. This study suggests that allogeneic BMT can be an effective therapy to achieve long-term control of acute leukemia, even in those patients who do not achieve a remission with primary therapy.     

Treatment of Refractory and Relapsed Adult Acute Leukemia Using a Uniform Chemotherapy Protocol

Twenty-nine adult patients with relapsed (21) or refractory (8) de novo acute leukemia (12 ALL and 17 ANLL) were treated with a remission-induction salvage chemotherapeutic protocol including vindesine, mitoxantrone, cyclophosphamide, intermediate-dose cytosine arabinoside, prednisolone and methotrexate. Ten of seventeen (59%) ANLL and 8/12 ALL (67%) achieved complete remission (CR). Seven of eight (86%) cases refractory to first-line remission-induction therapy (3/4 ANLL and 4/4 ALL) entered complete remission. The most frequent non-hematologic side effects were gastrointestinal. All patients experienced severe pancytopenia, with median times to recovery of granulocyte and platelet counts of 28 and 29 days, respectively. Nine of twenty-nine (31%) patients suffered febrile episodes of unknown origin and 13/29 (45%) suffered documented infections. Five patients (17%) died while aplastic, four from infection and one from cardiotoxicity. Four patients who entered CR were submitted to a bone marrow transplantation (BMT), two autologous and two allogeneic BMT. Sixteen of the 18 patients who entered CR relapsed, with a median remission duration of 3.5 ± 2.9 months. Two patients remain in remission at 5+ and 17+ months. These results suggest that this protocol is an effective remission-induction salvage therapy for adult acute leukemias.     

Correlation of chromosome abnormalities with patient characteristics, histologic subtype, and induction success in children with acute nonlymphocytic leukemia

Cytogenetic analyses of bone marrow cells were performed in 195 children with acute nonlymphocytic leukemia (ANLL) at diagnosis, as part of Childrens Cancer Study Group Study No. 251. Ninety-six patients (49%) exhibited clonal abnormalities, including trisomy 8 in 18 patients, t(8;21) in 11, t(15;17) in seven, loss of a sex chromosome in seven, monosomy 7 in seven, and the Philadelphia chromosome in four. Clonal abnormalities were found significantly more often in younger patients. Furthermore, recurring cytogenetic abnormalities tended to correlate with specific ages. For example, t(8;21) was associated significantly with children over four years of age, while -7 associated with overall loss of genetic material from the long arm of chromosome 7 (7q) and 11q- were associated significantly with younger children. Recurring chromosome abnormalities also correlated with specific ANLL histologic subtypes, such as t(8;21) with acute myelogenous leukemia and t(15;17) with acute promyelocytic leukemia. Presence or absence of cytogenetic abnormalities was compared with the ability of patients to achieve remission. Individuals exhibiting clonal abnormalities in bone marrow cells had an equally likely chance of achieving remission (74%) as those individuals with normal karyotypes (75%). Nonrandom chromosome abnormalities associated with a high induction success rate included +8 with a 94% induction success rate (P = .13) and t(8;21) with a 91% success rate (P = .46). Patients exhibiting the -7 abnormality associated with overall loss of 7q had a significantly less successful induction outcome, with only 28% achieving remission (P = .02); three of seven patients with t(15;17) died during induction therapy.     

ALL-TRANS RETINOIC ACID (ATRA) IN THE TREATMENT OF ACUTE PROMYELOCYTIC LEUKEMIA (APL)

Acute promyelocytic leukemia is characterized by the reciprocal translocation of chromosomes 15 and 17. All-trans retinoic acid (ATRA) efficiently induces differentiation of the abnormal promyelocytes. In this study, we had used ATRA as the primary induction therapy for 17 newly diagnosed patients, and as the salvage therapy for 11 patients who relapsed from or were resistant to chemotherapy. All patients received subsequent consolidation chemotherapy. Complete remission (CR) rate, early death rate (within 28 days of diagnosis) were then compared to an historical control of 50 APL patients treated with combination chemotherapy; and event-free survival of the 17 newly diagnosed patients was compared to the historical control. In the ATRA group, 26 of the 28 patients (93 per cent) attained complete remission. Two of 28 (7 per cent) died within 28 days of ATRA therapy. There was no case of primary resistance to ATRA. Combination chemotherapy was added to ATRA in five patients due to rapidly increasing leucocyte count. There was one case of retinoic acid syndrome which resolved with steroid. When compared to the 50 cases of historical control, there is significant improvement in the overall CR rate (92 per cent versus 59 per cent, p=0·001) and a significant reduction in the early mortality rate (7 per cent versus 41 per cent, p=0·001). Moreover, when the survival result of the 17 newly diagnosed patients were compared with the control, there is a significant improvement in the projected EFS at 3 years (64 per cent versus 25 per cent, p=0·007). In conclusion, ATRA was showm to improve the CR rate, reduce induction mortality and significantly prolong the event-free survival.     

Successful marrow transplantation for acute myelocytic leukemia following therapy for Hodgkin's disease

Five patients with acute myelocytic leukemia (AML) after combined modality therapy for Hodgkin's disease (HD) were treated with cyclophosphamide and busulfan followed by bone marrow transplantation (BMT). Four patients received allogeneic transplants from histocompatibility locus antigen (HLA)-compatible siblings and the fifth patient received an autologous marrow treated with 4-hydroperoxycyclophosphamide. Two patients died of complications of acute graft-v-host disease (GVHD) despite prophylaxis with either low-dose cyclophosphamide or cyclosporine. The remaining three patients were alive and disease-free 382, 617, and 620 days after transplant. These initial results are encouraging and more patients with treatment-related AML need to be evaluated with both allogeneic and autologous BMT to fully elucidate the potentially curative role of this intensive therapy in an otherwise fatal hematologic malignancy.     

Erythrocyte mean corpuscular volume during cytotoxic therapy is a predictive parameter of secondary leukemia in Hodgkin's disease

Mean corpuscular volume (MCV) evolution during cytotoxic therapy was studied in 32 patients with Hodgkin's disease (HD) who developed therapy-related acute nonlymphocytic leukemia (t-ANLL) and in 64 HD controls matched for age, therapy duration, and MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) administration. Maximum MCV during therapy reached 108.3 +/- 8.2 fl in t-ANLL patients and 103.4 +/- 9.1 fl in the controls (P = 0.001). Maximum MCV increase was 26.7 +/- 8.3 fl in t-ANLL patients and 16.6 +/- 8.3 fl in the controls (P = 10(-9). The greatest 3-month increase observed during therapy was 14.8 +/- 6 fl in the t-ANLL patients and 10.1 +/- 4.8 fl in the controls (P = 0.0001). During initial MOPP therapy, the greatest 3-month increase reached 14.1 +/- 5.3 fl in t-ANLL patients and 9.8 +/- 4.5 fl in the controls (P = 0.01). The relative risk of developing t-ANLL was 9 for a MCV maximum increase over 24 fl during therapy, which was observed in 71% of the patients with t-ANLL and in only 22% of the controls. For the greatest 3-month MCV increase over 15 fl observed in 57% of the t-ANLL patients and in 17% of the controls, the relative risk reached 15. This suggests that there is at least one factor, independent from therapy, which predisposes to t-ANLL. MCV evolution during therapy appears useful in determining which HD patients have a high risk of developing t-ANLL.     

Prospective study of 90 children requiring treatment for juvenile myelomonocytic leukemia or myelodysplastic syndrome: a report from the Children's Cancer Group.

PURPOSE: We report the first large prospective study of children with myelodysplastic syndrome (MDS) and juvenile myelomonocytic leukemia (JMML) treated in a uniform fashion on Children's Cancer Group protocol 2891. PATIENTS AND METHODS: Ninety children with JMML, various forms of MDS, or acute myeloid leukemia (AML) with antecedent MDS were treated with a five-drug induction regimen (standard or intensive timing). Patients achieving remission were allocated to allogeneic bone marrow transplantation (BMT) if a matched family donor was available. All other patients were randomized between autologous BMT and aggressive nonmyeloablative chemotherapy. Results were compared with patients with de novo AML. RESULTS: Patients with JMML and refractory anemia (RA) or RA-excess blasts (RAEB) exhibited high induction failure rates and overall remission of 58% and 48%, respectively. Remission rates for patients with RAEB in transformation (RAEB-T) (69%) or antecedent MDS (81%) were similar to de novo AML (77%). Actuarial survival rates at 6 years were as follows: JMML, 31% +/- 26%; RA and RAEB, 29% +/- 16%; RAEB-T, 30% +/- 18%; antecedent MDS, 50% +/- 25%; and de novo AML, 45% +/- 3%. For patients achieving remission, long-term survivors were found in those receiving either allogeneic BMT or chemotherapy. The presence of monosomy 7 had no additional adverse effect on MDS and JMML. CONCLUSION: Childhood subtypes of MDS and JMML represent distinct entities with distinct clinical outcomes. Children with a history of MDS who present with AML do well with AML-type therapy. Patients with RA or RAEB respond poorly to AML induction therapy. The optimum treatment for JMML remains unknown.     

Bone marrow transplantation in cancer patients

Bone marrow transplantation (BMT) has been done as one mode of cancer therapy which has the possibility of curing some cancer patients. In Nagoya, more than half of leukemia patients who received allogeneic BMT in a remission state became long-term survivors, and autologous BMT for acute lymphoblastic leukemia has been successfully done using monoclonal antibodies for purging leukemia cells from bone marrow. According to our experiences with leukemia BMT, the following essential conditions for performing successful BMT in cancer patients were discussed, 1) preconditioning therapy for eradication of cancer cells, 2) supportive care for prevention of side effects of BMT including virus infections such as cytomegalovirus, and 3) compatibility of HLA antigens.     

Specific chromosomal abnormalities in acute nonlymphocytic leukemia correlate with drug susceptibility in vivo

Specific chromosomal abnormalities are independent predictors of response to therapy in acute nonlymphocytic leukemia (ANLL) de novo. In a series of 149 patients with ANLL, we sought to determine whether the t(8;21), t(15;17), t(9;11) or other abnormalities of the long arm of chromosome 11, inv(16) or t(16;16), inv(3) or t(3;3), trisomy 8, and abnormalities of chromosome 5 (-5/5q-) or of chromosome 7 (-7/7q-) identify differences in susceptibility to chemotherapy drugs in vivo. The immediate outcome of the first cycle of remission induction chemotherapy was analyzed for patients in each cytogenetic subgroup as an index of the drug susceptibility of the leukemia cells in vivo. Patients with t(8;21), inv(16), t(16;16), or 11q abnormalities had high rates of complete remission after initial therapy (60-100%), whereas patients with -7/7q- or -5/5q- had low initial response rates (0-36%), suggestive of drug resistance in vivo. In general, cytogenetic groups with high initial complete remission rates ("drug sensitive") also had long disease-free survivals; those groups with low initial remission rates ("drug resistant") had short remission durations even if these patients eventually achieved complete remission with further therapy. Patients with acute promyelocytic leukemia (APL), all of whom had the t(15;17), were the exception; despite low initial remission rates, they had long disease-free survivals, possibly due to a more rapid cytotoxic effect of chemotherapy on the clonogenic APL cells than on the more numerous malignant promyelocytes. We conclude that the prognostic importance of specific chromosomal abnormalities in ANLL resides in part in differing susceptibilities to chemotherapy.     

Cytogenetic study in therapy-related myelodysplastic syndromes (t-MDS) and acute non-lymphocytic leukaemia (t-ANLL)

A cytogenetic study was performed in 27 patients suspected of t-MDS or t-ANLL. In 12 patients the diagnosis of t-MDS or t-ANLL was confirmed by morphological, cytochemical and immunophenotypical analysis. The cases were classified as RA (one), RAEB (four), CMML (two), ANLL (five). They had received chemotherapy and/or RT for Hodgkin's disease (eight cases), solid tumours (three cases) and multiple myeloma (one case). Clonal chromosome abnormalities were found in bone marrow or peripheral blood cells in all the 12 cases. Five patients had a clonal abnormality of chromosome no. 5 (monosomy, deletions, translocation and inversion of 5q). The critical region on chromosome no. 5 comprised bands q12-q34. Monosomy and deletion of chromosome 7q was observed in the other two patients. In the six remaining patients various karyotypic patterns were observed including a t(4;11) (q21;q23) in one case, monosomies (four cases) and trisomies (one case) of different chromosomes. In the other 15 cases, the presence of a normal karyotype together with the morphological and immunophenotypical characterisation was consistent with a diagnosis of non-neoplastic specimens.     

Chronic myelomonocytic leukemia: clinical features, cytogenetics, and prognosis in 30 consecutive cases

A retrospective analysis of 30 patients with chronic myelomonocytic leukemia (CrMML) was performed to define the natural history of the disease and the risk of acute transformation. Our patients fulfilled the following criteria of diagnosis: blood monocytosis over 1 X 10(9)/l, blast cell percentage in bone marrow up to 30, and in peripheral blood less than 5. The most common presenting feature was anemia; seven patients had fever; three patients complained of purpura and bleeding. Anysopoikilocytosis and macrocytosis were frequent. Abnormal granulocyte morphology, defective granulation and abnormal leukocyte alkaline phosphatase were often observed. Blast cells in peripheral blood smears were found in 14 patients. Serum and urine lysozyme levels were increased in 82 per cent and 93 per cent, respectively. Dysplastic changes involving erythroid, granulocytic and megakaryocytic lineages were constant features in all cases. Agranulated blasts above 5 per cent of marrow nucleated cells were seen in 13 patients (43 per cent). Seven of the 20 patients showed non-specific chromosomal abnormalities at diagnosis. Median survival from diagnosis was 18 months (range, 3-112). Evolution into acute myeloid leukemia occurred in 11 patients. No difference in survival was found between patients who developed acute leukemia and patients who did not. A shorter survival has correlated to the following parameters: leukocytes greater than 10 X 10(9)/l, the presence of blasts in peripheral blood and agranulated blasts in the marrow above 5 per cent.