High-dose carmustine, etoposide, and cisplatin and autologous bone marrow transplantation for relapsed and refractory lymphoma.

PURPOSE: We determined the toxicity and efficacy of a new preparative autologous bone marrow transplantation (ABMT) regimen in patients with relapsed or refractory non-Hodgkin's lymphoma or Hodgkin's disease. PATIENTS AND METHODS: Forty-four non-Hodgkin's lymphoma and 35 Hodgkin's disease patients 16 to 63 years of age were given intravenous carmustine (BCNU) 600 to 1,050 mg/m2, etoposide 2,400 to 3,000 mg/m2, and cisplatin 200 mg/m2 (BEP) and ABMT. Fifty-nine patients also received 15 to 20 Gy local radiation (involved-field radiotherapy [RI]) to active or previously bulky (> 5 cm) disease sites. RESULTS: Nonhematologic toxicities included nausea, vomiting, high-tone hearing loss, stomatitis, esophagitis, diarrhea, and hepatic and pulmonary toxicity. Two patients died within 40 days of marrow infusion as a result of sepsis and one patient died 7 months after transplant as a result of pulmonary fibrosis. Complete remissions (CRs) were noted in 72% (n = 57) of patients (n = 33 non-Hodgkin's lymphoma; n = 24 Hodgkin's disease). Forty patients (51%) remained alive and disease-free (n = 24 non-Hodgkin's lymphoma; n = 16 Hodgkin's disease) at a median of 17 (range, 8 to 57) months after marrow reinfusion. CONCLUSIONS: This regimen seems to be effective for relapsed lymphoma patients whose disease continues to exhibit chemotherapy sensitivity (16 of 24 [67%] disease-free). Furthermore, this regimen seems to be effective in patients who have never attained a CR (seven of 19 [37%] disease-free).

High-dose cyclophosphamide without stem-cell rescue for refractory CIDP.

Four patients with chronic inflammatory demyelinating polyneuropathy (CIDP) who were refractory to conventional treatment were treated with high-dose cyclophosphamide (200 mg/kg over 4 days). All improved in functional status and muscle strength. Nerve conduction studies improved in three of four. Other immunomodulatory medications have been discontinued. High-dose cyclophosphamide can be given safely to patients with CIDP and patients with disease persistence after standard therapy may have a response that lasts for over 3 years and results in long-term disease remission.

Treatment of chronic myelogenous leukemia with allogeneic bone marrow transplantation after preparation with busulfan and cyclophosphamide (BuCy2): an update.

Allogeneic bone marrow transplantation (BMT) has been shown to result in long-term disease-free survival in patients with leukemia. However, the utility of this treatment approach is limited by treatment-related morbidity and mortality. We present an update of a study in which a BMT preparative regimen consisting of a 4-day course of busulfan and a 2-day course of cyclophosphamide (BuCy2) was used in patients with chronic myelogenous leukemia. Patient survival depended on disease stage, with a 58% survival rate for patients in first chronic phase, 41% for those in accelerated phase, and 25% for those in the blast transformation stage. There was a significant difference in patient survival between those who received transplants within 1 year of diagnosis and those who received transplants more than 1 year after diagnosis (70% v 40%). This difference appeared to be due to the extent of previous exposure to busulfan. The overall mortality rate in this study was 46%. We conclude that the BuCy2 preparative regimen is similar in effectiveness to regimens that include total body irradiation and results in comparable levels of transplant-related mortality. Our results strongly indicate that patients with chronic myelogenous leukemia who receive BMT within the first year after diagnosis have a significantly better clinical outcome than those who receive BMT later in the course of the disease.

Comparison of preparative transplantation regimens using carmustine/etoposide/cisplatin or busulfan/etoposide/cyclophosphamide in lymphoid malignancies.

Most bone marrow transplantation preparative regimens use total body irradiation as one component. Recently, however, two non-total body irradiation containing autologous bone marrow transplantation preparative regimens have been evaluated in patients with lymphoid malignancies. The first regimen consisted of carmustine, etoposide, and cisplatin; some patients also received involved-field radiotherapy to sites of prior disease. Of the 79 patients with relapsed or refractory lymphoma who participated in this study, 57 (72%) achieved a complete remission and 40 (51%) remain in complete remission. Treatment-related deaths occurred in five patients (6%). The second preparative regimen evaluated consisted of busulfan, etoposide, and cyclophosphamide and included 21 patients with Hodgkin's lymphoma, non-Hodgkin's lymphoma, or acute lymphocytic leukemia. Sixteen patients (76%) achieved complete remission and 12 (57%) remain disease free. The regimen-related mortality rate in this study was 14%. The three treatment-related deaths were all due to pulmonary toxicity. The results of these clinical trials indicate that both the carmustine/etoposide/cisplatin regimen and the busulfan/etoposide/cyclophosphamide regimen are effective in treating lymphoid malignancies. Treatment-related toxicities and deaths are significant, but not prohibitive. Accordingly, these new preparative regimens deserve further evaluation in the treatment of patients with lymphoma or leukemia.

Allogeneic bone marrow transplantation for acute myelogenous leukemia, acute lymphocytic leukemia, and multiple myeloma following preparation with busulfan and cyclophosphamide (BuCy2).

The combination of busulfan (Bu) and cyclophosphamide (Cy) has been found to be effective preparative therapy for patients treated with allogeneic bone marrow transplantation (BMT). We developed the BuCy2 regimen, which contains a lower dose of cyclophosphamide than the original BuCy regimen, in the hope of reducing regimen-related toxicities. We have studied the use of BuCy2 as preparation for allogeneic BMT in patients with acute myelogenous leukemia, acute lymphocytic leukemia, and multiple myeloma. In patients with acute myelogenous leukemia, the leukemia-free survival and regimen-related toxicity rates obtained in our study appear similar to those achieved with other preparative regimens, including those containing Cy and total body irradiation (TBI). BuCy2 is also an effective BMT preparative regimen in patients with acute lymphocytic leukemia and multiple myeloma. Treatment with BuCy2 results in a lower incidence of severe stomatitis and probably of interstitial pneumonia than does treatment with Cy/TBI, but hepatic veno-occlusive disease occurs more frequently in BuCy-treated patients. The incidence of veno-occlusive disease appears to be affected by agents used as prophylaxis for graft-versus-host disease. Compared with Cy/TBI regimens, BuCy treatment is likely to result in fewer delayed effects of treatment, such as impairment of fertility and second malignancies. Current clinical efforts are focusing on ways to improve the antileukemic activity of the BuCy preparative regimen and to reduce regimen-related toxicities.

Extramedullary blast crisis in a patient with chronic myelogenous leukemia in complete cytogenetic and molecular remission on interferon-alpha therapy.

We report the previously undescribed occurrence of extramedullary blast crisis in a patient with chronic myelogenous leukemia in complete cytogenetic and molecular remission on interferon-alpha. Development of bilateral testicular swelling prompted a biopsy showing stromal infiltration with CD20 and TdT positive immature cells. On repeated examinations, the bone marrow remained BCR/ABL negative by RT-PCR analysis. However, the cerebrospinal fluid (CSF) contained atypical lymphocytes positive for the P210 BCR-ABL product. Following treatment with testicular irradiation, intrathecal methotrexate, systemic chemotherapy and an unrelated donor transplant, the patient showed no evidence of disease until 9 months post-transplant, when he relapsed in lymphoid blast crisis in both bone marrow and CSF.

Syngeneic marrow transplantation in multiple myeloma.

Two cases of IgA multiple myeloma treated with syngeneic bone marrow transplant and a non-total body irradiation (TBI) conditioning regimen are reported. Both patients presented with stage III disease which responded to standard chemotherapeutic management. The myelo-ablative program for transplant consisted of busulfan and cyclophosphamide (Bu/Cy). Evaluation at 40 days post-transplant revealed no evidence of residual myeloma in either patient. One patient died of disseminated Aspergillus fumigatus at day 73 post-transplant. The other patient relapsed at 18 months post-transplant. This conditioning regimen shows efficacy in aggressive myeloma and could be considered earlier in the disease.

Outcome of patients requiring medical ICU admission following bone marrow transplantation.

Despite encouraging results seen following bone marrow transplantation (BMT), it has been observed that once these patients become critically ill and require medical intensive care unit (MICU) admission, the chances of survival are poor. We hypothesized that while mechanical ventilation would be an important predictor for death in the MICU, those patients not requiring mechanical ventilation could be successfully discharged from the MICU. The records of 36 patients with 43 admissions to the MICU following BMT were analyzed. Of these admissions, 33 (76.7 percent) patients had allogeneic and 10 (23.3 percent) had autologous transplants, respectively. Overall, 14 (32.6 percent) of the admissions resulted in a satisfactory discharge from the MICU. There was no significant difference in the survival rates between those patients undergoing allogeneic or autologous transplantations, 11 (33.3 percent) vs 3 (30.0 percent), respectively. Twenty-seven (62.8 percent) of the admissions resulted in mechanical ventilation and were performed in 20 (66.7 percent) patients with allogeneic BMTs and 7 (70.0 percent) patients with autologous BMTs, which was not significantly different. The survival rate for those requiring mechanical ventilation was significantly less than for those not mechanically ventilated during their MICU stay, 1 (3.7 percent) vs 13 (81.3 percent), respectively (p < 0.001). Those patients who did not survive their MICU stay had a significantly higher mean APACHE II score of 21.2 +/- 4.7 than the survivors' score of 15.8 +/- 3.8 (p < 0.001). The average length of stay for the survivors was 4.4 + 3.0 days, which was significantly less than the 17.8 +/- 24.0 days for those patients not surviving (p < 0.001). These data indicate that admission to the MICU may result in a beneficial outcome for critically ill patients with BMTs, but for those requiring mechanical ventilation due to respiratory failure, the chances of survival are poor. This information may be useful for providing patients with BMTs and their families with realistic estimates of prognosis prior to transfer to the MICU and mechanical ventilation.

Bronchiolitis obliterans after autologous bone marrow transplantation.

Two patients are reported who underwent autologous bone marrow transplantation for lymphoma and developed rapidly progressive respiratory insufficiency at posttransplant (PT) days 90 and 273. Clinical examination revealed persistent cough, exertional dyspnea, inspiratory rales, and expiratory wheezing. Results of pulmonary function studies were consistent with rapidly progressive severe respiratory disease in both patients. Despite aggressive immunosuppressive therapy, both patients had a progressive decline in respiratory function and died of respiratory insufficiency at PT days 400 and 446, respectively. Each patient had histologic evidence of bronchiolitis obliterans (BrOb). These cases demonstrate that life-threatening obliterative bronchiolitis is not limited to patients undergoing allogeneic bone marrow transplantation, but can also follow autologous transplant. Awareness that this group is also at risk for BrOb and severe respiratory compromise may lead to early diagnosis and treatment.

Tretinoin for the treatment of cutaneous graft-versus-host disease.

Chronic graft-versus-host disease (GVHD) of the skin is a common complication of allogeneic bone marrow transplantation. It can be resistant to common methods of systemic immunosuppression. We report successful treatment of a patient with progressive cutaneous GVHD that was resistant to cyclosporine and steroids after allogeneic marrow transplantation for acute myelogenous leukemia using topical tretinoin (Retin-A).

Sexual dysfunction prior to high-dose chemotherapy and bone marrow transplantation.

A number of studies have suggested that high-dose chemotherapy and bone marrow transplantation may be associated with a variety of abnormalities of psychological function including sexual dysfunction. However, few studies have prospectively evaluated the association between sexual dysfunction and BMT. In particular, there are very little baseline data about sexual function immediately before transplant. The sexual function of 30 patients was assessed immediately prior to high-dose chemotherapy and bone marrow transplantation using the Derogatis Interview for Sexual Functioning (DISF) for males and females. More than 80% of patients had hematological malignancies; more than half were allograft recipients. Forty-seven percent of patients were found to have global sexual dysfunction and 60% had abnormalities of at least one parameter of sexual function. Forty-seven percent were dissatisfied with their sex life. Sexual dysfunction was associated with ejaculatory problems (P < 0.02) and erectile problems (P = 0.06) but not with amenorrhea. There was an association between cancer-related psychological problems and sexual dysfunction. A control group of inpatients with cancer had a similar incidence of sexual dysfunction (53% vs 47%, P = NS) suggesting that the tumor and its therapy were the major reasons for the sexual problems and not the prospect of transplant per se. This study emphasizes the need for baseline (pre-BMT) studies of quality of life and psychological function in BMT patients. We conclude that sexual dysfunction is a common finding prior to BMT; whether intervention can reduce this problem requires further study.

Bone marrow transplantation following busulfan and cyclophosphamide for acute myelogenous leukemia.

Twenty-five consecutive patients with acute myelogenous leukemia (AML) underwent 26 allogeneic bone marrow transplants at Hahnemann University Hospital. Marrow ablation for all patients consisted of busulfan 16 mg/kg and cyclophosphamide 120 mg/kg (BUCY2). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methylprednisolone. Seventeen transplants were performed during first remission and the rest during subsequent remission or relapse. All patients engrafted and all but one achieved a complete remission (CR) following a short period of aplasia. Twenty-two of 25 patients are alive. All 17 patients with AML transplanted in first CR are alive and 15 of these patients are in sustained hematologic remission with an estimated 2-year disease free survival of 85%. The estimated 2-year disease free survival is 70% for all patients followed for a median of 622 days (range 134-1533). Acute GVHD of grades 2-4 occurred in 23% of these patients. Toxicities of the regimen including interstitial pneumonitis, veno-occlusive disease (VOD) and hemorrhagic cystitis were minimal. There were no treatment related deaths. These results demonstrate that BUCY2 should be considered as a preparative regimen for allogeneic bone marrow transplantation for patients with AML in first remission.

Unrelated donor bone marrow transplantation without T cell depletion using a chemotherapy only condition regimen. Low incidence of failed engraftment and severe acute GVHD.

Twenty-five patients with hematologic malignancies were treated with busulfan (16 mg/kg) and cyclophosphamide (50 mg/kg x 3 days) as conditioning for bone marrow transplantation using marrow from serologically matched, DR locus genotypically identical unrelated donors. Previous studies of BuCy2 as conditioning for UD-BMT have reported a graft failure rate of up to 21% suggesting it may be insufficiently immunosuppressive in this setting. We elected not to use BuCy4 as it may have a higher incidence of extramedullary toxicity. In addition the patients received GM-CSF (500 mg/m2) from day 0, cyclosporine and short-course methotrexate (15 mg/m2 x 1, then 10 mg/m2 x 3) as GVHD prophylaxis and prophylactic ganciclovir at engraftment if either they or their donor were CMV antibody positive. The median age of the 25 patients was 41 years and the most common diagnosis was CML (76%). Seven patients were considered poor risk and eight males were recipients of marrow from female donors. Sixteen patients survive at a median of 435 days from transplant. The actuarial overall and disease-free survivals at 1 year in this group of older patients were 62 +/- 20% and 57 +/- 20% and 100-day survival was 70%. The engraftment rate was 100%; there have been no instances of secondary graft failure. Fifteen patients (60%) developed grade II-IV GVHD and 12 of 16 (75%) developed some chronic GVHD but only half of these were extensive. The performance status of survivors is good (median of 90); seven of 12 eligible patients are back at work. This study demonstrates that UD-BMT can be successfully performed in very closely HLA-matched older patients using a chemotherapy-only protocol and that low rates of severe acute GVHD can be achieved without T cell depletion.

Unrelated allogeneic bone marrow transplantation using high-dose busulfan and cyclophosphamide (BU-CY) for the preparative regimen.

This study reviews results of a radiation-free preparative regimen consisting of busulfan and cyclophosphamide in 65 unrelated allogeneic bone marrow transplant recipients. Thirty-eight patients had chronic myelogenous leukemia (17 patients chronic phase, 13 patients accelerated phase, eight patients blast phase), 19 patients had acute leukemia (second complete remission or relapse) and eight patients had myelodysplasia. The patients were transplanted at four different medical centers from July 1988 to November 1992. Ages ranged 4-48 years (median 32). Fifty-seven patients received busulfan 16 mg/kg and cyclophosphamide 120 mg/kg, and eight received busulfan at doses between 15 and 17 mg/kg and cyclophosphamide at doses 100-200 mg/kg as preparative regimens. All patients received cyclosporine for graft-versus-host disease prophylaxis; in addition 46 patients received corticosteroid, 38 methotrexate, six anti-CD5 ricin A-immunotoxin, and four T cell-depleted bone marrow. Median follow-up of survivors was 53 months (range 15-68 months). Four year actuarial survival was 24 +/- 12%. Four-year survival based on disease was 29 +/- 27% for chronic myelogenous leukemia (CML) in chronic phase, 20 +/- 9% for chronic myelogenous leukemia in accelerated phase, 0% for chronic myelogenous leukemia in blast phase, 32 +/- 40% for acute leukemia, and 38 +/- 34% for myelodysplasia. Actuarial survival was 66 +/- 40% in patients age < 20 years, vs 23 +/- 13% for patients ages 20 to 40, and 10 +/- 14% for patients age > 40 years. Fifty patients (88%) engrafted. Graft failure occurred in eight patients. Acute graft-versus-host disease grade II-IV occurred in 36 (72%). Two patients relapsed after engraftment with the donor cells and died of leukemia within a month of relapse. The most common causes of death were graft-versus-host disease (37%), and transplant-related toxicity (59%); relapse (4%) was a rare cause of death. Busulfan/cyclophosphamide is an effective preparative regimen in unrelated bone marrow transplantation permitting adequate engraftment and a low relapse rate. Best results are observed in patients less than 20 years old.

Autologous bone marrow transplantation for advanced stage mycosis fungoides.

Patients with advanced stage cutaneous T cell lymphoma (CTCL) have a median survival of 2-5 years with no currently available curative therapy. This limited pilot study was performed to determine if CTCL patients could undergo autologous bone marrow transplantation (ABMT) as a curative treatment without developing life-threatening infections. Since selection of a chemotherapeutic regimen is essentially empirical at this time, several drug combinations were screened. Total skin electron beam radiotherapy was used prior to transplantation to control the skin disease of four patients. Six patients have been transplanted and all have engrafted normally. Infections that developed after transplantation responded to conventional therapy and were typical of those observed in other patients undergoing ABMT. Five of the six patients had a complete clinical response to ABMT but three of these responses lasted less than 100 days. Two recent patients who were treated with carmustine, etoposide, and cisplatin are alive more than 1 year after transplantation without evidence of active disease. Thus, although this study does not prove the efficacy of ABMT, it does demonstrate that patients with CTCL can undergo ABMT without developing life-threatening infections and that carmustine-etoposide-cisplatin plus ABMT should be evaluated in subsequent studies to treat patients with poor prognosis CTCL.

Extramedullary toxicity of a conditioning regimen containing busulphan, cyclophosphamide and etoposide in 84 patients undergoing autologous and allogenic bone marrow transplantation.

Relapse is still a common problem after bone marrow transplant (BMT) and teh value of adding etoposide to standard conditioning agents is being tested. The aim of the study was to assess the extramedullary toxicity which resulted from adding etoposide to busulphan 16 mg/kg and cyclophoshamide 120 mg/kg (BuCY2). Eighty four patients received etoposide 40 mg/kg in addition to BuCY2 as conditioning for autologous and allogeneic BMT for leukemia and lymphoma. The Bearman system of grading extramedullary toxicity was used along with a system of grading skin toxicity that we devised. There were seven acute toxic deaths (8%) and in total 15 patients experienced life-threatening or fatal toxicity. The major finding was a striking increase in pulmonary toxicity with six deaths (five alveolar hemorrhage and one pulmonary embolus). Five of seven of the patients with severe pulmonary toxicity had been given irradiation to the lung fields (P < 0.001). Thirty nine per cent of patients had veno-occlusive disease of the liver but the case fatality rate was low (1 of 33). Dermatologic toxicity was experienced by 82% of patients and was symptomatically troublesome but rapidly reversible. The addition of etoposide to BuCY2 increases non-hematological toxicity. This regimen is associated with severe pulmonary toxicity in patients with a history of prior chest irradiation. A high incidence of skin toxicity was seen; a system for describing this toxicity is proposed.

Transient high grade heart block following autologous bone marrow infusion.

We performed a retrospective analysis of 42 consecutive patients undergoing autologous BMT to determine the incidence of second and third degree heart block following the infusion of cryopreserved autologous bone marrow and to identify any predisposing characteristics. A decrease in heart rate > or = 10 beats/min was observed in 80.5% of patients, with a mean decrement of 27 +/- 7 beats/min. 48.8% of patients developed absolute bradycardia (< or = 60 beats/min). Four of 41 patients (9.7%) experienced high-grade heart block: 9.7% second degree and 4.8% third degree. Heart block patients did not differ from the non-heart block group with respect to age, interval from diagnosis or bone marrow harvest to transplant, cardiac risk factors, pretransplant electrocardiograms or radionuclide angiograms, transplant chemotherapy regimens or serum chemistry values. There was an increased incidence of heart block in patients with prior exposure to cyclophosphamide (p < 0.05) and vinca alkaloids (p < 0.05). There appears to be a high incidence of transient second and third degree heart block following autologous marrow infusion. This may be related to prior chemotherapy, but more likely is an effect of the infusate itself. Predisposing factors were not identified.

Hepatic dysfunction following busulfan and cyclophosphamide myeloablation: a retrospective, multicenter analysis.

Veno-occlusive disease continues to be a significant cause of morbidity and early mortality following bone marrow transplantation. This study retrospectively analyzes the incidence and risk factors for severe VOD in 350 patients treated with 4 days of busulfan (total 16 mg/kg) and 2 days of cyclophosphamide (120 mg/kg) at four marrow transplant centers. Using the criteria defined by McDonald et al (Hepatology 1984; 4: 116-122), 93/350 (27%) developed VOD (11% mild, 5% moderate and 11% severe). Multivariate analysis revealed the following risk factors to be significantly associated with severe VOD: pretransplant transaminase and alkaline phosphatase elevation, ciprofloxacin antibiotic prophylaxis, use of estrogen/progestins or vancomycin during the peritransplant period and methotrexate for GVHD prophylaxis. Mild to moderate grades of VOD were not associated with significantly increased mortality but mortality was higher in patients with severe VOD (31%, P = 0.0013). These data suggest that risk factors for VOD may depend on the preparative regimen used and suggest that use of these risk factors may identify a subgroup of patients that can be targetted for studies of prevention of VOD.

Economic analysis of conventional-dose chemotherapy compared with high-dose chemotherapy plus autologous hematopoietic stem-cell transplantation for metastatic breast cancer.

We performed an economic analysis of data from 180 women in a clinical trial of conventional-dose chemotherapy vs high-dose chemotherapy plus stem-cell transplantation for metastatic breast cancer responding to first-line chemotherapy. Data on resource use, including hospitalizations, medical procedures, medications, and diagnostic tests, were abstracted from subjects' clinical trial records. Resources were valued using the Medicare Fee Schedule for inpatient costs at one academic medical center and average wholesale prices for medications. Monthly costs were calculated and stratified by treatment group and clinical phase. Mean follow-up was 690 days in the transplantation group and 758 days in the conventional-dose chemotherapy group. Subjects in the transplantation group were hospitalized for more days (28.6 vs 17.8, P=0.0041) and incurred higher costs (US dollars 84055 vs US dollars 28169) than subjects receiving conventional-dose chemotherapy, with a mean difference of US dollars 55886 (95% CI, US dollars 47298-US dollars 63666). Sensitivity analyses resulted in cost differences between the treatment groups from US dollars 36528 to US dollars 75531. High-dose chemotherapy plus stem-cell transplantation resulted in substantial additional morbidity and costs at no improvement in survival. Neither the survival results nor the economic findings support the use of this procedure outside of the clinical trial setting.

Cytogenetics and cell surface marker analysis in chronic myelocytic leukemia. II. Implications for patient management.

Chronic myelocytic leukemia (CML) is a model system for the study of many aspects of malignant disease. One aspect that correlates with decreasing therapeutic response is tumor progression. This progression is often accompanied by clonal evolution. In those cases where aggressive therapy does not prevent this evolution, the clinical response to therapy usually proves to be poor and of short duration. Investigators are concentrating their efforts in three primary, but not mutually exclusive, areas with respect to the clinical management of CML. These include: an attempt to distinguish patients at risk for early transformation from those who will have a prolonged chronic phase; the cryopreservation of autologous bone marrow or buffy coat early in chronic phase for subsequent use in the accelerated phase and; endeavors to identify early markers for disease progression allowing intervention before an irreversible blast crisis occurs. This report deals with two types of potential prognostic markers of transformation: chromosomal and cell surface characteristics. The appearance of nonrandom abnormal chromosomal patterns has been correlated with myeloblastic transformation by many investigators. However, there has always been a subset of CML patients who do not undergo clonal evolution. Additionally, the type(s) of transformation in CML may vary depending on the cell lineages involved. Unlike myeloblastic transformants, many of our patients who do not exhibit clonal evolution as a concomitance of disease progression develop a lymphoblastic transformation. Cytofluorometric analysis can distinguish small populations of abnormal cells with lymphoblastic characteristics (HLA DR+). Initial data suggests that patients expressing the HLA DR+ in their "normal" peripheral blood cells are at risk of undergoing lymphoblastic transformation. The combined use of clinical, cytogenetic, and cytofluorometric data to predict an impending transformation and to discriminate between myeloblastic and lymphoblastic populations allows clinicians to manage their patients more effectively.