Initial Induction Chemotherapy Research Articles

Clinical and cellular pharmacology in relation to solid tumours of childhood

Our understanding of the clinical and cellular pharmacology of drugs commonly used in the treatment of childhood cancer have increased greatly over the past two decades. However, with the exception of childhood acute lymphoblastic leukaemia (ALL), our current knowledge of factors such as inter-patient pharmacokinetic variability and cellular determinants of chemosensitivity has not been utilized in the design of integrated clinical studies. Recent pre-clinical and clinical evaluation of the topoisomerase I inhibitors topotecan and irinotecan has highlighted the potential importance of pharmacological factors in their effectiveness as cytotoxics. In this review, the clinical and cellular pharmacology of vincristine, actinomycin D, doxorubicin, cyclophosphamide, ifosfamide, cisplatin, carboplatin and etoposide will be discussed in relation to the major paediatric solid tumours. For each disease type, knowledge of the clinical and cellular pharmacology of a candidate drug will be related to pharmacodynamic responses such as response, toxicity and prognosis. For diseases such as Wilms’ tumour, osteogenic sarcoma and Ewing’s tumour, histological response to initial induction chemotherapy is of prognostic significance, and the depth of response is increasingly recognised as an important determinant of prognosis for high-risk neuroblastoma. For several of these tumour types, the dose-intensity of chemotherapy may be an important variable in determining prognosis. However the relationship between pharmacokinetic variability, cellular pharmacology and the major determinants of chemosensitivity to those drugs employed in first line therapy is unknown. The study of these relationships, by means of up front window studies in children who present with high-risk disease, may be as important as the introduction of new agents. Indeed, the optimisation of current therapies may be required to allow a fully informed selection of those children for whom novel therapies are truly needed. Funding and international collaboration at the clinical and scientific level would be required to achieve these aims.

Bilateral Cavitary Pulmonary Consolidations in a Patient Undergoing Allogeneic Bone Marrow Transplantation for Acute Leukemia

A 10-year-old boy developed severe dyspnea and respiratory failure during a hospitalization for an allogeneic unrelated bone marrow transplantation for acute myeloid leukemia. He had first presented 23 weeks earlier with acute myeloid leukemia and had not responded to the initial induction chemotherapy. Next, he was successfully treated with another regimen of remission-induction chemotherapy without complications. He received an allogeneic unrelated bone marrow transplant after a conditioning regimen of cyclophosphamide (Endoxan; AstaMedica BV; Diemen, the Netherlands) therapy, total body irradiation, and low-dose antithymocyte globulin. Both donor and recipient were seronegative for cytomegalovirus. Immediately after transplantation, the patient received therapy with cyclosporine A, short-course methotrexate, and total bowel decontamination. During this time, he was nursed in a protective environment. Seven days after undergoing the bone marrow transplantation, he developed a fever. A blood culture revealed a coagulase-negative Staphylococcus infection for which he was treated with IV antibiotics (ceftazidime and teicoplanin). Six days later (13 days after the bone marrow transplantation), a chest radiograph showed bilateral pulmonary infiltrates (Fig 1).

Aspergilosis cutánea secundaria en paciente inmunodeprimido

Abstract—Aspergillosis is a opportunistic fungal infection that is usually seen in immunocompromised patients with neutropenia and sometimes the skin is affected.A 44 years old woman diagnosed of acute myelogenous leukemia who was receiving initial induction chemotherapy, on day +25 the induction period she presented fever and necrotic nodules in trunk and extremities. On histologic study numerous septate braching hyphae are seen within the dermis and on microbiology culture grow Aspergillus niger. In TAC of high resolution a little nodule on the right lung was found as the primary focus of the infection. The diagnosis of secondary cutaneous aspergillosis was made. The patient was treated with lyposomal anfotericine (iv) and oral voriconazole, all the lesions disappeared.

Bone marrow transplantation for children with acute myelogenous leukaemia in the first complete remission

Of 52 children aged 9 months to 16 years old with acute myelogenous leukaemia (AML) in first complete remission undergoing bone marrow transplantation at our institution, 31 received allogeneic transplants (allo-BMT) and 21 received autologous transplants (ABMT). Initial induction and consolidation chemotherapy were not uniform. BMT was performed at a median of 7 months (range: 2.5 to 22.5 months) from the diagnosis. Conditioning included chemotherapy ( n=43: 4×4 mg/kg of busulfan and 3×60 to 70 mg/m 2 of melphalan) or total body irradiation (12 Gy) plus chemotherapy ( n=9). Graft-versus-host disease (GVHD) prophylaxis in allo-BMT cases consisted of methotrexate±cyclosporin A. Unpurged marrow was used in ABMT cases. All patients showed sustained engraftment. Amongst allograft cases, acute or chronic GVHD developed in 7 patients each (23%). 8 patients (15%) died (5 with allo-BMT, 3 with ABMT), including transplant-related mortality in 3 of the allo-BMT patients. 7 patients had relapses (3 with allo-BMT, 4 with ABMT). As of June 1999, 43 patients are alive and well 13 to 160 months after BMT (median, 71), with 5-year disease-free survival rates after BMT of 84% for allo-BMT, 81% for ABMT and 83% altogether. Although the presented data are based on a retrospective evaluation, we consider BMT for childhood AML during first complete remission an effective treatment for eradicating leukaemia.

Eosinophilic myelodysplasia transforming to acute lymphoblastic leukaemia.

A 43 year old male presented with a marked eosinophilia and associated systemic symptoms. A diagnosis of myelodysplasia was made on the basis of bone marrow morphology and karyotype. Over...

Adult acute myeloid leukaemia: update on treatment.

Adult acute myeloid leukaemia (AML) is uncommon, with an age-standardised incidence of approximately 3 per 100,000. Patients present (median age, > 60 years) with evidence of bone marrow failure, anaemia, leukopenia or thrombocytopenia and their sequelae, or AML is detected incidentally by a full blood count. Treatment for AML aims to eliminate leukaemia from bone marrow with intensive chemotherapy: age (over or under 60 years) and performance status determines whether standard or high-dose chemotherapy can be used, but fewer than half the patients with AML are under 60 years. Supportive therapy during initial induction chemotherapy is needed to control neutropenic sepsis and thrombocytopenic bleeding, and to ameliorate the side effects of chemotherapy. Standard induction chemotherapy produces complete remission in 56%-74% of patients; 20% are long term survivors; 10%-15% of patients die in the induction period. Allogeneic haemopoietic stem cell transplantation is recommended in patients under 50 years with an HLA- compatible sibling, with the best outcomes achieved in patients transplanted in first complete remission. It can also provide long term survival in patients who fail to achieve remission after induction therapy. The outcome of AML has improved, particularly for younger patients, but treatment outcomes for older patients and those with secondary leukaemia are still unsatisfactory. The mean overall survival of patients in randomised studies treated with standard therapy is still only 9-15 months.

Functional Expression of Fas (CD95) in Acute Myeloid Leukemia Cells in the Context of CD34 and CD38 Expression: Possible Correlation With Sensitivity to Chemotherapy

AbstractClinical studies of bone marrow transplantation (BMT) suggest that the immune system contributes to the eradication of acute myeloid leukemia (AML). A recent study also showed that the Fas (CD95/APO1) mediates apoptotic signal from cytotoxic T lymphocytes. Sixty-four patients with AML were studied for the expression of Fas in the context of CD34 and CD38 coexpression. The clinical relevance of Fas expression and function on AML was also investigated. Fas was expressed on 2% to 98% of AML cells (2% to 20% in 11 patients, 20% to 50% in 20 patients, 50% to 80% in 24 patients, and 80% to 98% in nine patients). Only 44.4% of patients with AML M1 (French-American-British [FAB] classification) were Fas+ (≥20% of leukemia cells expressed Fas), whereas 89.1% of patients with AML M2, M3, M4, M5 were Fas+ (P < .01). Among 43 CD34+ patients (≥20% leukemia cells were CD34+), 34 were Fas+, and 19 of 21 CD34− patients were Fas+ (P = NS). Thirteen cases were studied for their expression of Fas in the context of CD34 and CD38 using three-color analysis. Fas is expressed at a high level in the gated CD34+CD38± and CD34+CD38+ population. In 10 AML samples, Fas was expressed at a higher level in CD34+/CD38+ population than in CD34+/CD38± or CD34− cell populations. Fas-induced apoptosis by anti-Fas monoclonal antibody (MoAb) was determined by morphologic features and colorimetric DNA fragmentation assay. Induction of apoptosis was found in 14 of 24 cases. However, no statistically significant correlation was observed between Fas expression and induction of apoptosis. Leukemia colony-forming unit assays suggested that in some cases, Fas-induced apoptosis occurred in the clonogenic cell populations. Parameters such as laboratory and clinical data at initial diagnosis were correlated with Fas expression and only response to initial induction chemotherapy showed significant correlation with Fas expression (P < .05). We conclude that the majority of AML cells exhibit variable expression of Fas, and apoptosis could be induced by anti-Fas MoAb in some cases. Our results suggest the Fas-mediated apoptosis may be clinically relevant, whereas the issue of clonogenic leukemia cells and Fas expression needs further studies.

Functional Expression of Fas (CD95) in Acute Myeloid Leukemia Cells in the Context of CD34 and CD38 Expression: Possible Correlation With Sensitivity to Chemotherapy

Clinical studies of bone marrow transplantation (BMT) suggest that the immune system contributes to the eradication of acute myeloid leukemia (AML). A recent study also showed that the Fas (CD95/APO1) mediates apoptotic signal from cytotoxic T lymphocytes. Sixty-four patients with AML were studied for the expression of Fas in the context of CD34 and CD38 coexpression. The clinical relevance of Fas expression and function on AML was also investigated. Fas was expressed on 2% to 98% of AML cells (2% to 20% in 11 patients, 20% to 50% in 20 patients, 50% to 80% in 24 patients, and 80% to 98% in nine patients). Only 44.4% of patients with AML M1 (French-American-British [FAB] classification) were Fas+ (≥20% of leukemia cells expressed Fas), whereas 89.1% of patients with AML M2, M3, M4, M5 were Fas+ (P &lt; .01). Among 43 CD34+ patients (≥20% leukemia cells were CD34+), 34 were Fas+, and 19 of 21 CD34− patients were Fas+ (P = NS). Thirteen cases were studied for their expression of Fas in the context of CD34 and CD38 using three-color analysis. Fas is expressed at a high level in the gated CD34+CD38± and CD34+CD38+ population. In 10 AML samples, Fas was expressed at a higher level in CD34+/CD38+ population than in CD34+/CD38± or CD34− cell populations. Fas-induced apoptosis by anti-Fas monoclonal antibody (MoAb) was determined by morphologic features and colorimetric DNA fragmentation assay. Induction of apoptosis was found in 14 of 24 cases. However, no statistically significant correlation was observed between Fas expression and induction of apoptosis. Leukemia colony-forming unit assays suggested that in some cases, Fas-induced apoptosis occurred in the clonogenic cell populations. Parameters such as laboratory and clinical data at initial diagnosis were correlated with Fas expression and only response to initial induction chemotherapy showed significant correlation with Fas expression (P &lt; .05). We conclude that the majority of AML cells exhibit variable expression of Fas, and apoptosis could be induced by anti-Fas MoAb in some cases. Our results suggest the Fas-mediated apoptosis may be clinically relevant, whereas the issue of clonogenic leukemia cells and Fas expression needs further studies.

Neoadjuvant and adjuvant chemotherapy in the multidisciplinary treatment of oral cancer stage III or IV.

We performed a retrospective analysis on the effect of initial induction chemotherapy with two courses of cisplatin (each course 120 mg/m2 cisplatin on day 1, then 20 mg/m2 bleomycin (alone) per day for 5 days with 4 weeks between courses) in 75 consecutive patients with advanced cancer of the oral cavity or lip. Further local therapy consisted of surgery or radiation, depending on tumour location. In 18 resected patients adjuvant chemotherapy was added. This consisted of carboplatin, 400 mg/m2 on day 1 then ftorafur alone, 500 mg/m2/day for 30 consecutive days, repeated every month for 4 consecutive months. Among the patients treated in the neoadjuvant setting, complete response was observed in 10 out of 75 patients (13%), and partial response in a further 50 patients (67%) (partial plus complete rate 80%). Of all the patients, 43% in stage III and 26% in stage IV were long-term survivors. Improved survival was observed in surgical patients where adjuvant postoperative chemotherapy was added (P < 0.025). The main toxic effect was vomiting, observed in 71 patients. We noted a low rate of stomatitis (4%) and an important hearing loss (12%). Neoadjuvant and adjuvant cisplatin-based chemotherapy as part of a multidisciplinary approach have a high overall response rate and low toxicity, and should increase survival in cancer of the oral cavity or lip.

Treatment of pediatric genitourinary malignancy with interstitial brachytherapy: Peter MacCallum Cancer Institute experience with four cases

To describe early outcome and technical treatment aspects of four patients with pediatric genitourinary malignancy receiving local therapy using interstitial brachytherapy at the Peter MacCallum Cancer Institute since 1991. Two patients with primary bladder tumors and two patients with primary vaginal tumors received interstitial brachytherapy with needle-template techniques following chemotherapy. Two patients were treated for salvage following local failure after primary chemotherapy and two patients electively after initial induction chemotherapy, one following limited surgical excision. Three patients were treated exclusively with brachytherapy with doses of 50-55 Gy (LDR), and one patient also received external beam radiation. Resultant implants, dosimetry, and dose prescriptions are described and illustrated. Follow-up is short (14-27 months), but all patients remain well without significant sequelae. One child required salvage surgery for local failure. Interstitial brachytherapy using needle-template techniques described is an ideal method of local ablative therapy for pediatric genitourinary malignancy. Functional and late sequelae should be less than that of radical surgery or external beam radiation. There are technical and practical advantages compared with other brachytherapy techniques described in the literature.

Management of Infection in Patients with Acute Leukemia

Substantial improvements have occurred in the infectious diseases management of patients with acute leukemia. It is now unusual for patients receiving initial induction chemotherapy at a major center to die of infectious complications without receiving an adequate course of antineoplastic treatment. Many patients also receive reinduction chemotherapy with prolonged periods of neutropenia without succumbing to major infectious complications. However, the area of management of infections in patients with acute leukemia has remained a dynamic process, with infection management issues that remain complex and controversial.

Limited small cell lung cancer of the lung treated with combination chemotherapy and radiotherapy: a retrospective analysis.

We assessed the outcome in 65 patients with limited small cell lung cancer (SCLC) treated from 1980 through 1989 with combination chemotherapy and chest and cranial irradiation. Of the 65 patients, 32.3% (21/65) achieved a complete remission (CR) prior to radiation therapy; six additional cases achieved a CR after radiotherapy with an improvement of 10% in the incidence of CR. In our group, 8 patients were alive and free of disease at 30 months (12.3%). We think that a combination of local thoracic irradiation in SCLC limited disease plus chemotherapy yields more CR and improves survival, especially in the group of patients who obtained the CR after initial induction chemotherapy.

Shedding of CD9 antigen into cerebrospinal fluid by acute lymphoblastic leukemia cells

The accurate identification of small numbers of leukemic cells in the cerebrospinal fluid (CSF) presents a diagnostic problem in the treatment of acute lymphoblastic leukemia (ALL). We demonstrated that soluble CD9 antigen was shed into CSF obtained from children with ALL, using enzyme-linked immunosorbent assay (ELISA), which used the activity of CD9 antigen to bind the Ricinus communis agglutinin (RCA1) and a monoclonal antibody, SJ-9A4, simultaneously. Using RCA1/SJ-9A4 ELISA, CD9 antigen was detectable in CSF but not in plasma from 12 cases of CD9+ ALL in central nervous system (CNS) relapse. However, CD9 antigen was not released into CSF from 11 cases of CD9- ALL with CNS involvement, 136 cases of CD9+ ALL in complete remission (CR), 29 cases of CD9- ALL in CR, or 21 cases of aseptic meningitis. Interestingly, the levels of CD9 antigen were elevated in CSF from 7 of 10 CD9+ ALL patients without cytologically proven CNS involvement at diagnosis, with subsequent return to undetectable levels after initial induction chemotherapy was begun. In addition, sequential analysis of CSF from a 5-year-old boy with CD9+ ALL in CNS relapse showed that levels of CD9 antigen correlated well with the number of leukemic cells in CSF. Serial quantitative analysis of CD9 antigen in CSF could be useful to detect the proliferation of residual leukemic cells before the clinical manifestation.

Shedding of CD9 Antigen Into Cerebrospinal Fluid by Acute Lymphoblastic Leukemia Cells

The accurate identification of small numbers of leukemic cells in the cerebrospinal fluid (CSF) presents a diagnostic problem in the treatment of acute lymphoblastic leukemia (ALL). We demonstrated that soluble CD9 antigen was shed into CSF obtained from children with ALL, using enzyme-linked immunosorbent assay (ELISA), which used the activity of CD9 antigen to bind the Ricinus communis agglutinin (RCA1) and a monoclonal antibody, SJ-9A4, simultaneously. Using RCA1/SJ-9A4 ELISA, CD9 antigen was detectable in CSF but not in plasma from 12 cases of CD9+ ALL in central nervous system (CNS) relapse. However, CD9 antigen was not released into CSF from 11 cases of CD9- ALL with CNS involvement, 136 cases of CD9+ ALL in complete remission (CR), 29 cases of CD9- ALL in CR, or 21 cases of aseptic meningitis. Interestingly, the levels of CD9 antigen were elevated in CSF from 7 of 10 CD9+ ALL patients without cytologically proven CNS involvement at diagnosis, with subsequent return to undetectable levels after initial induction chemotherapy was begun. In addition, sequential analysis of CSF from a 5-year-old boy with CD9+ ALL in CNS relapse showed that levels of CD9 antigen correlated well with the number of leukemic cells in CSF. Serial quantitative analysis of CD9 antigen in CSF could be useful to detect the proliferation of residual leukemic cells before the clinical manifestation.

An approach to intensive antileukemia therapy in patients with previous invasive aspergillosis

In an attempt to decrease the risk for reactivation of life-threatening invasive aspergillosis (IA) during subsequent myelosuppression in patients with previously diagnosed IA who were receiving antileukemic treatment, we evaluated the role of intensive antifungal therapy with amphotericin B and 5-fluorocytosine administered prophylactically throughout the antileukemic regimen and induced granulocytopenia to prevent IA reactivation without compromising the intensive chemotherapy. During a 30-month period, 10 patients with acute myelogenous leukemia and primary IA developing during initial antileukemia induction therapy and severe granulocytopenia (less than 100/mm3) underwent 14 subsequent courses of intensive marrow aplasia-producing chemotherapy during early complete remission or at leukemia relapse. All patients had evidence of ongoing IA healing by lung computerized tomography (CT) prior to reinstitution of intensive chemotherapy. Nine patients receiving 13 chemotherapy courses also received aggressive prophylactic anti-IA therapy with amphotericin B (1.0 mg/kg/day) and 5-fluorocytosine beginning at least 48 hours prior to antileukemia therapy institution and continued until the time of granulocyte recovery. All nine patients receiving aggressive antifungal therapy survived without clinical evidence of IA reactivation. Transient radiographic evidence of IA reactivation during granulocytopenia was detected by lung CT during two of the 13 chemotherapy courses. In contrast, the patient who did not receive anti-IA prophylaxis had both clinical and radiographic evidence of IA reactivation during severe granulocytopenia and died. Anti-IA prophylaxis was achieved without irreversible nephrotoxicity, prolonged marrow suppression, alteration of antileukemia treatment, or negative impact on clinical outcome relative to acute leukemia. This approach of antifungal prophylaxis in adults with acute leukemia and documented primary IA occurring during initial induction chemotherapy has been successful in preventing clinically significant IA reactivation during subsequent granulocytopenic courses, and allows for administration of additional intensive antileukemia therapy.

悪性リンパ腫の診断と治療に関する研究

A comparison was made between the therapeutic outcome of patients with diffuse large-cell non-Hodgkin's lymphoma treated with combination chemotherapy containing adriamycin (adriamycin regimen) and those treated with combination chemotherapy not containing adriamycin (non-adriamycin regimen). All the patients had no prior therapy, and there were no differences in any other background factors between the two treatment groups. Of 32 patients on the non-adriamycin regimen, 19 (59%) achieved complete response (CR) and 12 (38%) achieved partial response (PR). Of 20 patients on the adriamycin regimen, 14 (70%) achieved CR and 6 (30%) achieved PR. For those on the non-adriamycin regimen, the median duration of CR was 10 months, the projected 5-year relapse-free rate was 27%; the median survival time for all patients was 1 year 7 months; and the projected 5-year survival rate was 24%. For those on the adriamycin regimen, a median duration of CR was not reached, the projected 5-year relapse-free rate was 85%; the median survival time for all patients was 1 year 11 months; and the projected 5-year survival rate for all patients was 58%. These results show the superiority of combination chemotherapy containing adriamycin, indicating that adriamycin is a essential agent for the initial induction chemotherapy for the large-cell type of non-Hodgkin's lymphoma.

Common acute lymphoblastic leukemia characterized by four different DNA stemlines with heterogeneity in RNA content, antigen expression and sensitivity to chemotherapy

Four subpopulations of cells with different DNA content were present in the bone marrow of a pediatric patient with acute lymphoblastic leukemia. Flow cytometry of DNA/RNA and DNA/surface antigen expression enabled the identification and characterization of diploid, hypertriploid, tetraploid and hypertetraploid leukemic cells. This was not appreciated by cytogenetic analysis, which identified only some tetraploid cells ( 3 20 metaphases). Common acute lymphoblastic leukemia antigen was expressed in all aneuploid and also on 17% of diploid cells. Quantitative CALLA expression was unrelated to ploidy and cell size. Cellular RNA content paralleled ploidy, i.e. the more aneuploid cells had increased RNA content and there was pronounced RNA heterogeneity within each DNA stemline. The different subclones showed almost identical stages of early B-cell differentiation. The early pre B-cell antigens BL1 and BL2 were expressed in approx. 80 and 60%, respectively, of aneuploid leukemic cells. Cytoplasmic immunoglobulin heavy chain was also present. Clonal excess of lambda light chain immunoglobulin on the cell surface was present on less than 10% of hypertriploid, tetraploid and hypertetraploid leukemic cells indicating differentiation of a subpopulation of aneuploid leukemic cells to mature B cells. This was not seen for any diploid cells. The heterogeneity of the different subpopulations was also evident in the differences in response to chemotherapy: the hypertriploid and hypertetraploid subpopulations were most sensitive to initial induction chemotherapy.

Prospective randomized trial of antibiotic prophylaxis in acute leukemia

Patients undergoing initial remission induction chemotherapy for acute leukemia in a protected environment unit were randomly assigned to parenteral antibiotic prophylaxis or oral and parenteral antibiotic prophylaxis. Complete remissions were obtained in 82 percent of the 45 patients receiving oral and parenteral antibiotic prophylaxis and 76 percent of the 41 patients receiving parenteral antibiotic prophylaxis. Approximately 20 percent of the patients in both groups have had a continuous complete remission for more than five years. The episodes of fever of unknown origin and major infection were significantly more common in patients receiving parenteral antibiotic prophylaxis, although the episodes of local infection were similar in both groups. The duration of remission and survival was similar in both groups. Hence, the oral and parenteral antibiotic regimen was more effective for infection prophylaxis, but had no effect on response to antileukemic chemotherapy.

Phenotyping of canine lymphoma with monoclonal antibodies directed at cell surface antigens: classification, morphology, clinical presentation and response to chemotherapy.

Forty cases of naturally occurring canine lymphoma were studied using a panel of murine monoclonal antibodies which identify defined subsets of normal canine lymphocytes. The distribution of phenotypes was similar to that which is seen in man in that the majority (78 per cent) of canine lymphomas were of B-cell origin but a definite minority were phenotypically of T-cell (10 per cent) or non-B, non-T-cell (12 per cent) origin. The expression of Ia-like antigens was restricted to B-cell neoplasms. Within each histologic subgroup of canine lymphomas there was considerable heterogeneity of cell surface marker expression. Immunophenotype appeared to correlate with clinical presentation. Finally, the reactivity of lymphoma cells with murine monoclonal antibody DLy-6, an antibody which appears to react with a differentiation antigen on canine B and T cells, strongly predicted the outcome of initial induction chemotherapy in that all ten evaluable dogs with DLy-6-tumors achieved complete responses to initial chemotherapy while only four of 11 dogs with DLy-6+ tumors responded completely.

Identification of early relapsing patients with adult acute nonlymphocytic leukemia by bone marrow biopsy after initial induction chemotherapy.

Bone marrow biopsies obtained from 69 adult patients with acute nonlymphocytic leukemia (ANLL) six to 10 days after initial induction chemotherapy were reviewed blindly to detect the presence of residual leukemia. Discrimination between the presence or absence of leukemic cells was provided by assessment of the numbers, clustering, and nuclear morphology of blasts and promyelocytes. Twenty-six patients had frank leukemia, 25 had no apparent leukemic cells, and 18 had focal residual leukemia. Of 25 patients whose bone marrow contained no detectable residual leukemic cells, 21 gained complete remission without further chemotherapy. These patients had a median duration of remission of 278 days, with five patients still remaining in remission for 578-882 days. Similarly, all of the 18 patients who had focal residual leukemia achieved complete remission without additional chemotherapy; however, all have relapsed with a median duration of remission of 163 days. This study indicates that patients with foci of residual leukemia in their one-week posttreatment bone marrow samples readily achieve remission, but carry a substantial leukemic burden that increases the likelihood of early relapse.