High-dose cytosine arabinoside and mitoxantrone in previously-treated acute leukemia patients

35 patients with refractory or relapsed acute leukemia received salvage chemotherapy using high-dose cytosine arabinoside 2 g/m2 intravenously for 3 hours every 12 h, in 8 doses, followed by continuous infusion of mitoxantrone 12 mg/m2/day for 2 d. 9 patients had acute myeloblastic leukemia (AML), (4 relapsed, 5 refractory), 20 had acute lymphoblastic leukemia (ALL) (11 relapsed, 9 refractory) and 6 had chronic myelogenous leukemia (CML) in the blastic phase (BP). 4 out of 9 AML and 16 out of 20 ALL achieved complete remission. Median survival was 6 months for all patients and 10 months for responders. A short (1.5 months) chronic phase was achieved in 3 patients with CML. The main toxic effect was hematologic. A pharmacokinetic study was performed on mitoxantrone. No correlation was found with clinical response. The combination of mitoxantrone and ara-C is an effective antileukemic regimen, especially in ALL.     

Phase II evaluation of aclarubicin in refractory adult acute leukemia: a Southwest Oncology Group Study

Aclarubicin, a new anthracycline antibiotic, was used to treat 24 adult patients with refractory adult leukemia, using a total dose of 300 mg/m2 (75 mg/m2/day X 4). There were 20 patients with acute myelogenous and four with acute lymphoblastic leukemia. Approximately two-thirds of the patients had a Karnofsky score of less than or equal to 2, and two-thirds had received two or more previous induction programs. Interim bone marrow evaluation was obtained in 18 of 30 remission induction courses and revealed marked hypocellularity in 14, inadequate specimens in three, and persistent disease in one. Seven patients received more than one course. Two patients refused further therapy. In patients with myelogenous leukemia, there were two complete remissions lasting 10 and 16 months and one partial remission lasting 4 1/2 months. There were no responders in patients with lymphoblastic leukemia. Toxicity included profound leukopenia and thrombocytopenia, moderate nausea and vomiting, diarrhea, and mucositis. There were no cardiac symptoms associated with the drug infusion, but there were three late events possibly associated with anthracycline cardiotoxicity. Used in this dosage schedule, aclarubicin is an active, but toxic, agent in the acute myelogenous leukemias.     

Bone marrow transplantation for advanced acute leukemia: a pilot study of high-energy total body irradiation, cyclophosphamide and continuous infusion etoposide

Leukemic relapse following bone marrow transplantation (BMT) for acute leukemia is the most common cause of treatment failure. Because a more intensive pre-transplant preparative regimen may prevent disease recurrence we have designed a novel intensive conditioning regimen for BMT using high-energy total body irradiation (total dose 850 cGy; energy 24 MV; midplane received dose rate 26 cGy/min; day -6) followed by cyclophosphamide (dose 50 mg/kg/day; schedule 2-h infusion; days -5, -4, -3) and continuous infusion high-dose etoposide (dose 500 mg/m2/day; schedule: 22-h infusion; days -5, -4, -3). Between February 1987 and December 1988, 45 patients with advanced acute leukemia received transplants using this regimen. Twenty-five purged auto-transplants were done for B-lineage (n = 18), T-lineage (n = 6) or biphenotypic (n = 1) acute lymphoblastic leukemia, with 12 in remission and 13 in relapse at the time of transplantation. Of these, nine had non-relapse deaths and 16 have relapsed between 1 and 19 months (median 3 months) following transplantation. Of note all the T-lineage patients relapsed including two transplanted in remission and five transplanted in relapse. Nineteen patients received histocompatible allogeneic transplants and one underwent syngeneic transplantation. Of seven patients with acute lymphoblastic leukemia transplanted in refractory relapse, three have had an overt relapse, three died of interstitial pneumonitis and only one survives disease free 15 months after transplantation. Of 13 patients with acute non-lymphocytic leukemia and variants (11 who were transplanted in relapse) three died without relapse, three have relapsed and seven survive disease free from 9 to 27 months (median 20 months) after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Combination therapy with mitoxantrone and etoposide in refractory acute myelogenous leukemia

We have investigated the efficacy of mitoxantrone in combination with etoposide in patients with refractory acute myelogenous leukemia. The regimen consisted of 10 mg/m2/day of mitoxantrone given iv on Days 1-5; and 100 mg/m2/day of etoposide as short infusion, initially on Days 1-3 and extended to Days 4 and 5 as appropriate. Of the 26 patients treated with this combination, nine (34.6%) have achieved complete remission and two have achieved partial remission. The median duration of continuous complete remission was 85 days (range, 21-183+). Toxicity was mild and only one case of early death was observed. This combination seems to be an active regimen in refractory acute myelogenous leukemia, and its incorporation in front-line therapy seems warranted.     

Bone marrow transplantation for leukemia following a new busulfan and cyclophosphamide regimen

Busulfan 16 mg/kg and cyclophosphamide 120 mg/kg were used as conditioning prior to allogeneic marrow transplantation in 50 adult patients with acute nonlymphocytic leukemia (ANLL), acute lymphocytic leukemia (ALL), and chronic myelogenous leukemia (CML). A standard risk group of 20 patients included those with acute leukemia in remission and CML in chronic phase. A high-risk group of 30 patients included individuals with refractory acute leukemia, acute leukemia in relapse, acute leukemia following preleukemia, and CML in accelerated and blastic phase. Complete remission and sustained complete engraftment were achieved in all evaluable patients. The duration of aplasia was remarkably short (median of 8 days), resulting in a low infection rate during the period of neutropenia, a reduced need for blood product support, and a short length of hospital stay. Three-year actuarial relapse-free survival in both standard-risk (88.9% +/- 10.5%) and high- risk (50.5% +/- 9.6%) groups compares favorably with that reported with total body irradiation (TBI) containing regimens.     

Clinical studies with rubidazone.

One hundred and thirty-three patients, 94 with acute luekemia and 39 with solid tumors, received rubidazone, alone or in combination, at M. D. Anderson Hospital. The initial study, a phase I--II study carried out in 39 patients with acute leukemia, revealed substantial antileukemic activity with optimal results at a dose level of 450 mg/m2. Toxic manifestations included an acute reaction suggestive of histamine release with dose-limiting mucositis at a dose of 600 mg/m2. Forty-seven patients with acute leukemia were treated at phase II dose levels. Thirteen of 32 patients (42%) with acute myelogenous leukemia and seven of ten patients (70%) with acute lymphocytic leukemia achieved complete remission. Twenty-seven previously untreated patients with acute leukemia who were greater than 50 years old were treated with rubidazone in combination with cytosine arabinoside, vincristine, and prednisone. Fifteen patients (50%) achieved complete remission including 12 of 15 patients (73%) who were treated at a dose of 200 mg/m2 of rubidazone on Day 1 and a dose of 70 mg/m2/day X 7 days of cytosine arabinoside (continuous infusion). For patients with solid tumors, the dose-limiting toxic effect was myelosuppression at a dose of 200 mg/m2. Other toxicity at that dose level was minimal. The best responses were seen in patients with carcinoma of the period with two of four evaluable patients showing objective tumor regression. Of six previously untreated patients with thyroid carcinoma none responded, and in a phase II study of patients with breast cancer there were no partial remissions among 13 patients. Cardiac toxicity, manifested by congestive heart failure, occurred in seven patients at cumulative doses of 1050--2600 mg/m2 of rubidazone; all patients had had prior anthracycline therapy at low doses. Rubidazone has been shown to be an active antileukemic agent, but appears to be less active than Adriamycin in our studies of patients with solid tumors.     

Diaziquone given as a continuous infusion is an active agent for relapsed adult acute nonlymphocytic leukemia

Diaziquone given as a bolus has not been effective in patients with relapsed or refractory leukemia. Because of in vitro data suggesting enhancement of diaziquone-induced cytotoxicity for human and murine leukemia cells with increased duration of drug exposure and the relatively short terminal plasma half-life of diaziquone, 49 patients (34 acute nonlymphocytic leukemia [ANLL], six chronic myelogenous leukemia in blast crisis [CML-B], five acute lymphocytic leukemia [ALL], four 2 degrees ANLL) with leukemia were given diaziquone as a continuous infusion for seven days. The maximum tolerated dose was 28 mg/m2/d for seven days. The dose-limiting toxicity was the duration of bone marrow aplasia (median, 49 days to greater than 500 PMNs in responders; range, 28 to 101 days). Nonhematologic toxicity was minimal. Responses occurred only in patients with relapsed ANLL, of whom 26 were treated at effective doses. There were six complete responses (CR) (23%) and two partial responses (PR) (8%), although five of eight responders never achieved platelet counts greater than 100,000/microL. Thrombocytopenia in these patients was felt to be a manifestation of diaziquone effect, not persistence of leukemia. The median duration of CR was 195 days (range, 88 to 860+). One patient had active CNS leukemia at the start of treatment and has had a durable (28+ month) CR in both sites of disease. Diaziquone produced prolonged aplasia in patients with secondary ANLL and CML-B (five of ten patients died aplastic), whereas patients with ALL all had regrowth of leukemia and two failed to become aplastic. The lack of significant nonhematologic toxicity and the activity in patients with relapsed ANLL render diaziquone of interest as second-line therapy or consolidation therapy in first remission for patients with ANLL.     

Fractionated total body irradiation and high dose cyclophosphamide: a preparative regimen for bone marrow transplantation for patients with hematologic malignancies in first complete remission

Summary We treated 73 patients with hematologic malignancies in first complete remission (acute lymphoblastic leukemia = 23 patients; acute nonlymphoblastic leukemia = 25 patients; chronic myelogenous leukemia in first chronic phase = 20 patients, and high grade lymphoma = five patients) with a uniform preparative regimen consisting of fractionated total body irradiation (1 320 cGy) and high dose cyclophosphamide (100 mg/kg), followed by allogeneic bone marrow transplantation. By radiation dosimetry we demonstrated that the calculated doses were delivered accurately and reproducibly. Actuarial survival rates (± SEM) in complete remission were as follows: Acute lymphoblastic leukemia = 74±9%; acute nonlymphoblastic leukemia = 50±11%; and chronic myelogenous leukemia = 55±11%. Actuarial relapse rates for these three diagnoses were 19±9%, 17±11%, and 0% respectively. Three of the five lymphoma patients are alive in complete remission at 22+, 28+, and 54+ months. Overall probability of survival for the 73 patients was 59±7%. Interstitial pneumonia, usually associated with cytomegalovirus infection and graft-versus-host disease, and relapse of the underlying malignancy were the major causes of death.Abbreviations ALL Acute lymphoblastic leukemia - ANLL Acute non-lymphoblastic leukemia - AP Anterior-posterior - BMT Bone marrow transplantation - CML Chronic myelogenous leukemia - CMV Cytomegalovirus - CP Chronic phase - CR Complete remission - CSA Cyclosporine A - CY Cyclophosphamide - FTBI Fractionated total body irradiation - GVHD Graft-versus-host disease - IP Interstitial pneumonia - MTX Methotrexate - PA Posterior-anterior - Ph¹ Philadelphia chromosome - PSE Prednisone - TBI Total body irradiation - TLD Thermoluminescent dosimetry - UPN Unique patient number - WBC White blood cell count This work was supported by United States Public Health Service Grants CA 30206 and CA 33572 from the National Cancer Institute, DHHSSpecial Fellow of the Leukemia Society of America     

Phase II study of mitoxantrone and cytarabine in acute myeloid leukemia

Thirty-eight patients with acute myeloid leukemia (AML) were treated with mitoxantrone (Mto) combined with cytarabine (Ara-C). Five patients had received no previous treatment for acute myeloid leukemia, seven were refractory to treatment with standard first-line chemotherapy, eight had relapsed during treatment, and 18 had relapsed after treatment was stopped. Eleven of these relapses were early (within 6 months of stopping treatment). Mto was given for 5 days by iv bolus injection at a dose of 10 mg/m2 to 12 patients and at 12 mg/m2 to 26. Ara-C was given at a dose of 1 g/m2 twice daily by a 2-hour infusion for 3 days to 37 patients. One patient received Ara-C at a dose of 500 mg/m2 twice daily for 3 days. Toxicity was acceptable except for cerebellar toxicity in two patients, which was irreversible in one. Twenty-two patients (56%) achieved complete remission (CR), and four achieved partial remission (10%). Seventy-five percent of the patients who had relapsed during treatment and 58% of those who had relapsed after treatment was stopped achieved CR. Eleven patients remain in CR at a median time of 10 months (range, 3-17) after treatment. In five patients remissions have lasted greater than 1 year, one in a patient treated in second relapse and one in a patient treated in third relapse. Mto and Ara-C appear to be effective salvage therapy in acute myeloid leukemia and should be considered for incorporation into first-line induction regimens.     

Sequential intermediate-dose cytosine arabinoside and mitoxantrone for patients with relapsed and refractory acute myelocytic leukemia

Based on in vitro evidence of time-dependent synergistic kill of HL-60 leukemia cells exposed to Ara-C and mitoxantrone, 44 patients with relapsed or refractory AML and 3 with blastic CML were treated with a timed sequence of both drugs. There were 25 females and 22 males, with a median age of 53 (range 21-75). Of 31 patients with relapsed AML, 24 had one prior remission, 6 had two and 1 had three. Of these, 15 had failed a second reinduction attempt. Thirteen patients were primarily refractory to induction with Ara-C plus daunorubicin. Each dose of Ara-C, 500 mg/m2, was followed after 6 hr by mitoxantrone, 5 mg/m2, and the sequence was repeated four to six times (44-68 hr) in different cohorts of patients. All but two patients (one with blastic CML and one in relapse and refractory) are evaluable for response and toxicity. Of 16 patients in relapse without prior reinduction 7 achieved CR and 3 PR (62% response rate); there were 3 CR in the 14 patients who were in relapse and refractory (21% response rate) and 4 CR and 1 PR (35% response rate) in the 14 patients with primary anthracycline resistance. Five of seven patients previously exposed to mitoxantrone achieved CR. Response lasted from 2 to 42 months, with two patients alive and in continuing remission at 34 and 42 months. Average marrow recovery was seen after 25 days and time to remission was 30 days. Six patients died in induction (four from sepsis and two from the tumor lysis syndrome) and 21 had progressive disease. Chemotherapy was well tolerated with minor nausea and vomiting in 13 patients, moderate in 20, and severe in 2. Most patients did not have evidence of drug-induced mucositis: it was minor in 9 and moderate in 2. Renal dysfunction was attributable to the use of nephrotoxic antibiotics. Hepatic dysfunction was reversible and was minor in 10 patients, moderate in 13, and severe in 3. Sequential, timed administration of intermediate-dose Ara-C and mitoxantrone is an active and well-tolerated antileukemic regimen.     

Treatment of relapsed and refractory acute myeloid leukemia with diaziquone and mitoxantrone: a CALGB phase I study

Twenty-one patients with relapsed or refractory acute myeloid leukemia (AML) were treated with mitoxantrone (12 mg/m2/day, days 1-3) and diaziquone (continuous infusion days 1-5). The dosage of diaziquone was increased for sequential cohorts of seven patients from 20 mg/m2/day to 24 mg/m2/day, and finally to 28 mg/m2/day to determine the maximum tolerated dose for this chemotherapy combination. Myelosuppression was the dose-limiting toxicity. The median time to recovery of blood counts was greater at the highest dose of diaziquone (48 days) than at the lower two doses (31 and 28 days). Other toxic effects were minimal. Overall, 9/21 (43%, 95% confidence interval, 0.22 to 0.66) patients achieved complete remission. We conclude that this combination of drugs shows sufficient antileukemic activity with acceptable toxicity to warrant further trials.     

Mitoxantrone and continuous infusion of cytosine arabinoside in refractory and relapsed acute lymphoblastic leukemia.

Twenty adult patients with relapsed or refractory acute lymphoblastic leukemias (ALL) received a regimen employing two courses of mitoxantrone 12 mg/m2 by rapid intravenous infusion on days 1, 2 and 3 and cytosine arabinoside (ARA-C) 200 mg/m2/day by continuous infusion on days 1-7. Complete remission (CR) was achieved in 10 of 20 (50%) patients (3 refractory and 7 relapsed). Median duration of CR was 5 months (range 2-9). The treatment was associated with minimal extrahematologic toxicity, with no cardiac toxicity. Our results are nearly in line with therapeutic responses obtained with regimens employing megadose therapy (HD ARA-C). Because of acceptable toxicity, mitoxantrone plus continuous infusion of a standard dose of ARA-C could be considered for relapsed of refractory ALL patients eligible for an intensive therapeutic approach (bone marrow transplantation) after a second CR.     

Phase I study of busulfan, cyclophosphamide, and timed sequential escalating doses of cytarabine followed by bone marrow transplantation.

In both animal models and human studies in leukemia, residual disease on day 8 following myelosuppressive therapy is in a proliferative phase and therefore may be sensitive to the S-phase specific drug cytarabine. Based on this concept, 17 patients with refractory or relapsed leukemia or lymphoma undergoing either autologous or allogeneic bone marrow transplantation (BMT) were treated on a Phase I protocol using high doses of busulfan (16 mg/kg, days -10, -9, -8, -7) and cyclophosphamide (120 mg/kg, days -6, -5) followed by escalating doses of a 48-h continuous infusion of cytarabine (starting dose 1000 mg/m2/48 h, days -3, -2). Ten patients received autologous transplants (two with Hodgkin's disease, seven with non-Hodgkin's lymphoma, one with chronic myelogenous leukemia (CML) in blast phase). Seven received allogeneic BMT (two with refractory acute myelocytic leukemia (AML), one with refractory acute lymphoblastic leukemia (ALL) undergoing a second BMT, one with Burkitt's-type leukemia, one with ALL in fifth relapse and two with CML in accelerated/blast phase). Two of these patients received a T cell-depleted haploidentical transplant. The maximum tolerated dose of cytarabine was 1500 mg/m2/48 h; a pulmonary syndrome including dyspnea, hypoxemia, and interstitial infiltrates which responded to aggressive diuresis was the dose limiting toxicity. Of the 10 patients who received cytarabine doses of 2000 or 2500 mg/m2/48 h, five patients developed adult respiratory distress syndrome (ARDS) with three patients requiring intubation; two recovered. Of the nine patients with lymphoma, seven responded with complete tumor clearance (CTC) with two patients tumor-free 13 and 15 months post-BMT, one remained refractory and one died too early to evaluate (TETE).(ABSTRACT TRUNCATED AT 250 WORDS)     

Allogeneic bone marrow transplantation for hematological malignancies following therapy with high doses of busulphan and cyclophosphamide

Thirty patients with malignant hematological disease underwent allogeneic bone marrow transplantation following Busulphan (Bu) and Cyclophosphamide (Cy). The diseases were chronic myelogenous leukemia, acute lymphoblastic and non lymphoblastic leukemia, myelofibrosis and multiple myeloma in complete remission and in relapse. A sustained disease-free survival (DFS) was achieved in 0/5 acute leukemia patients transplanted in relapse, in 5/7 acute leukemia patients transplanted in remission (600-1550 days) and in 6/9 CML patients transplanted in the chronic phase of the disease (500-950 days). A sustained DFS was also achieved in one 2nd BMT for relapsed CML. The data suggest that the Bu-Cy protocol combines high tumor ablative capability with toxicity comparable to previously described conditioning regimens for allogeneic BMT, particularly in diseases involving a great expansion of the bone marrow.     

Clofarabine, a novel nucleoside analog, is active in pediatric patients with advanced leukemia

Despite progress in leukemia therapy, most children who experience relapse have a dismal prognosis. New, effective approaches are needed. We conducted a phase 1 study of a novel nucleoside analog, clofarabine, in pediatric patients with refractory and relapsed leukemia. Clofarabine was infused intravenously over 1 hour each day for 5 days. Six dose levels, between 11.25 and 70 mg/m(2) per day for 5 days, were studied in 25 patients. A modified 3 + 3 phase 1 design was followed with 30% dose escalation until the dose-limiting toxicity (DLT) was defined. The maximum tolerated dose (MTD) was 52 mg/m(2) per day for 5 days. At the end of infusion at MTD, clofarabine triphosphate levels in leukemia blasts varied between 6 microM and 19 microM, which resulted in complete and sustained inhibition of DNA synthesis. The DLT was reversible hepatotoxicity and skin rash at 70 mg/m(2) per day for 5 days. Twenty-five patients were treated. Five patients achieved complete remission (CR), and 3 achieved partial remission (PR), for an overall response rate of 32%. Clofarabine is well tolerated and shows significant antileukemic activity in heavily pretreated children. Multicenter phase 2 trials in pediatric acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) are ongoing.     

Fractionated total body irradiation and high-dose VP 16-213 followed by allogeneic bone marrow transplantation in advanced leukemias

Thirty-eight patients (median age, 21 years) with acute nonlymphoblastic leukemia (ANLL) (17 patients), acute lymphoblastic leukemia/lymphoma (ALL) (18 patients), chronic myelogenous leukemia (two patients), and refractory anemia received allogeneic bone marrow transplants from HLA-identical sibling donors or a one-antigen- mismatched brother (one patient) after a preparatory regimen consisting of fractionated total body irradiation and high-dose VP 16-213 (60 to 70 mg/kg body weight). Of the 33 patients with acute leukemia who received grafts from HLA-identical donors, three patients with ANLL received transplants in first remission and one patient with standard- risk ALL received a graft while in second remission. All other patients were in more advanced stages of their disease or exhibited other high- risk features. At the time of analysis, 20 of the 33 patients were alive, with 19 of them remaining in continued complete remission for 6 to 35 months (median, 18 months). The 3-year actuarial disease-free survival rate of 56.6% +/- 9.7% (SE) and the actuarial relapse rate of 11.9% +/- 6.8% (SE) demonstrate that the combination of fractionated total body irradiation and high-dose VP 16 is an effective mode of therapy in patients with advanced leukemias. Preliminary experience cautions against the use of VP 16 instead of cyclophosphamide in any clinical situation carrying an increased risk of graft rejection because the immunosuppressive potency of VP 16 is largely untested but may be inferior to that of cyclophosphamide.     

Mitoxantrone and etoposide: an effective regimen for refractory or relapsed acute myelogenous leukemia

23 adult patients with refractory or relapsed acute myelogenous leukemia (AML) received salvage chemotherapy with mitoxantrone and etoposide. The regimen consisted of mitoxantrone, 10 mg/m2/d by 30-min infusion, and etoposide 100 mg/m2/d by 30-min infusion, given 12 h apart for 5 consecutive d. Of 23 patients treated, 13 met the criteria for highly refractory disease (6 primary resistant; 4 with early relapse during maintenance; 3 relapsed and refractory to reinduction). 10 patients had relapsed off-therapy more than 6 months after achieving first CR. Overall, 14 patients (61%) achieved a complete remission (CR): 6/13 (46%) with refractory AML, and 8/10 (80%) with relapsed AML. 2 patients had a partial remission, 2 died in aplasia, and 5 were nonresponders. In responding patients, the median time for recovery of granulocyte count was 27 d. The most important nonhematologic side effect was oral mucositis, which was severe in 35% of cases. No signs of cardiac toxicity were observed. The median CR duration was 5 months (range, 2 to 12+ months). The combination of mitoxantrone and etoposide appears a highly effective and relatively well tolerated salvage regimen for refractory and relapsed AML. Its incorporation into first-line induction and consolidation programs for newly diagnosed AML patients should be considered.     

Serum lactic dehydrogenase (LDH) levels in acute leukemia: marked elevations in lymphoblastic leukemia

Serum total lactic dehydrogenase (LDH) levels were examined in 42 patients with acute leukemia, 9 patients with chronic myeloid leukemia, 6 of them in blastic crisis, and 53 patients with lymphoma and other lymphoproliferative disorders. The mean range of serum LDH leveles in Hodgkin's and non-Hodgkin's lymphoma was 402 +/- 210 IU/liter and 313 +/- 113 IU/liter, while that of patients with nonmalignant disorders was 308 +/- 74 IU/liter. In acute nonlymphoblastic leukemia (ANLL), the range was 126-684 IU/liter (mean value 413 +/- 146 IU/liter). In 6 of the patients (11.3%) with lymphoma and in 6 cases (26.8%) with ANLL, the LDH levels were above 500 IU/liter. None of these patients had levels over 900 IU/liter. Patients with acute lymphoblastic leukemia (ALL) had a range of 402-3582 IU/liter (mean value of 1669 + 1038 IU/liter). In 15 of the 19 patients (78.9%) with ALL, serum LDH values were above 900 IU/liter. In addition, 3 patients with chronic myeloid leukemia (CLM) in blastic crisis had levels of 970-1940 IU/liter. One of these 3 patients had lymphoblastic crisis, while the second case responded clinically to vincristine and prednisone, but was not regarded as ALL. The differences in serum LDH levels between ALL and ANLL are statisticaly significant (p < 0.001). It appears that markedly elevated serum LDH levels in acute leukemia are suggestive of ALL, and that in individual patients, the LDH levels were correlated with the number of blasts during remission and relapse.     

Amsacrine in refractory acute leukemia

Thirty-two patients with heavily pretreated, relapsed acute leukemia were treated with amsacrine (120 mg/m2/day X 5). The 32 patients received a total of 41 courses of therapy, and 31 patients were evaluable for response. There were no complete remissions and only one partial remission (3 months) in an adult patient with acute lymphoblastic leukemia. Toxic effects included myelosuppression (100% of the patients), hyperbilirubinemia (41%), nausea and vomiting (41%), stomatitis (9%), and cardiac dysrhythmia (3%). We conclude that amsacrine as a single agent is not a useful treatment for relapsed, heavily pretreated adult and pediatric acute leukemia.     

Fractionated total body irradiation and high-dose etoposide as a preparatory regimen for bone marrow transplantation for 99 patients with acute leukemia in first complete remission

Ninety-nine consecutive patients with acute leukemia in first complete remission under age 50 (median age 27 years; age range 1 to 47 years) with a histocompatible sibling donor were treated with fractionated total body irradiation (1,320 cGy) and high-dose etoposide (60 mg/kg) followed by allogeneic bone marrow transplantation. Sixty-one patients were diagnosed with acute myelogenous leukemia (AML), 34 patients with acute lymphoblastic leukemia (ALL), 3 patients with biphenotypic acute leukemia, and 1 patient with acute undifferentiated leukemia. Thirty of the 34 patients with ALL had at least one of the following high-risk factors: age greater than 30, white blood cell count at presentation > 25,000/microL, extramedullary disease, certain chromosomal translocations, or the need for greater than 4 weeks of induction chemotherapy to achieve first complete remission. Cumulative probabilities of disease-free survival and relapse at 3 years were 61% and 12%, respectively, for the 61 patients with AML and 64% and 12%, respectively, for the 34 patients with ALL. By stepwise Cox regression analysis, significant prognostic variables for patients with acute myelogenous leukemia were the presence of acute graft-versus-host disease and increasing age, whereas for patients with acute lymphoblastic leukemia, significant variables were age and the development of cytomegalovirus-associated interstitial pneumonia. Complications related to graft-versus-host disease and relapse of leukemia were the major causes of death.