Venous thromboembolism prevention during asparaginase-based therapy for acute lymphoblastic leukemia.

BACKGROUND: Venous thromboembolism (vte) is a recognized complication in patients treated with asparaginase-containing chemotherapy regimens; the optimal preventive strategy is unclear. We assessed the safety and efficacy of prophylaxis using low-dose low molecular weight heparin in adult patients with acute lymphoblastic leukemia in complete remission treated with an asparaginase-based post-remission chemotherapy regimen. METHODS: As part of the intensification phase of the Dana-Farber Cancer Institute 91-01 regimen, asparaginase was administered weekly to 41 consecutive patients for 21-30 weeks; these patients also received prophylaxis with enoxaparin 40 mg daily (60 mg for patients ≥80 kg). Outcomes were assessed against outcomes in a comparable cohort of 99 patients who received the same chemotherapy regimen without anticoagulation prophylaxis. RESULTS: The overall rate of symptomatic venous thrombosis was not significantly different in the prophylaxis and non-prophylaxis cohorts (18.92% and 21.74% respectively). Among patients receiving prophylaxis, vte occurred in higher proportion in those who weighed at least 80 kg (42.86% vs. 4.35%, p = 0.0070). No major bleeding complications occurred in the prophylaxis group (minor bleeding: 8.1%). CONCLUSIONS: Prophylaxis with low-dose enoxaparin during the intensification phase was safe, but was not associated with a lower overall proportion of vte.

Do quality of life or physical function at diagnosis predict short-term outcomes during intensive chemotherapy in AML?

BACKGROUND: Intensive chemotherapy (IC) used to treat acute myeloid leukemia (AML) is associated with toxicity, particularly in older adults. Emerging data suggest that baseline quality of life (QOL) and physical function may predict outcomes in oncology, although data in AML are limited. We investigated the association between baseline QOL and physical function with short-term treatment outcomes in adults and elderly AML patients. MATERIALS AND METHODS: We conducted a prospective, longitudinal study of adults (age 18+) AML patients undergoing IC. Before starting IC, patients completed the European Organisation for the Research and Treatment of Cancer (EORTC) 30-item questionnaire (QLQ-C30) and Functional Assessment of Cancer Therapy Fatigue subscale (FACT-Fatigue) in addition to physical function tests (grip strength, timed chair stands, 2-min walk test). Outcomes included 60-day mortality, intensive care unit (ICU) admission and achievement of complete remission (CR). Logistic regression was carried out to evaluate each outcome. RESULTS: Of the 239 patients (median age 57.5 years), 56.7% were male and median Charlson comorbidity score was 0. Sixty-day mortality, ICU admission and CR occurred in 9 (3.7%), 15 (6.3%) and 167 (69.9%) patients, respectively. Using univariate regression, neither QOL nor physical function at presentation was predictive of 60-day mortality (all P > 0.05), whereas ICU admission (P < 0.001) and remission status at 30 days (P = 0.007) were. Fatigue (P = 0.004) and role functioning (P = 0.003) were predictors of ICU admission; QOL and physical function were not. A higher Charlson score predicted ICU admission (P = 0.01) and remission status (P = 0.002). The cytogenetic risk group was associated with achievement of CR (P = 0.02); QOL and physical function were not (all P > 0.05). Findings were similar when patients age 60+ were examined. Relationships between fatigue and role functioning with ICU admission deserve further exploration. CONCLUSIONS: Baseline QOL and physical function tests in this prospective study were not associated with short-term mortality, ICU admission or achievement of CR after the first cycle of chemotherapy.

Adolescents with acute lymphoblastic leukemia treated at pediatric versus adult hospitals.

BACKGROUND: The objective was to compare 5-year overall survival (OS) between adolescent and young adult (AYA) patients (age 15-19) with acute lymphoblastic leukemia (ALL) treated at a pediatric versus an adult center. PATIENTS AND METHODS: This was a population-based analysis using administrative data of Ontario ALL AYA patients diagnosed between 1986-2009. We calculated predicted survival proportions (PSPs) and 95% confidence intervals (CI). We also surveyed sites to determine whether pediatric or adult-based protocols were used in each period. RESULTS: Overall, 290 patients between 15-19 years of age were diagnosed with ALL during the study period; 144 patients (49.7%) were treated at an adult center. When adjusted for gender, age, income quintile and time period, AYA patients treated at a pediatric center did not have a significantly different PSP (0.65, 95% CI: 0.56-0.75) in comparison to those treated at an adult center (0.62, 95% CI 0.52-0.73; P = 0.87). Most AYA patients treated at adult centers received pediatric protocols in the recent periods. CONCLUSIONS: Using population-based data, AYA ALL patients had similar outcomes whether treated at a pediatric or an adult center. Early introduction of aggressive treatment protocols in adult centers may have negated differences in outcomes among AYA patients by site of care.

Long-term recovery of quality of life and physical function over three years in adult survivors of acute myeloid leukemia after intensive chemotherapy.

We previously described impairments in quality of life (QOL) and physical function among acute myeloid leukemia (AML) survivors between diagnosis and 1 year. The aim of the current study is to describe and compare to normative data QOL and physical function recovery over 3 years from diagnosis and treatment with intensive chemotherapy (IC). At assessments done at baseline (pre-IC) and at 11 time points over 3 years, QOL, fatigue, and 3 physical performance measures (PPMs; grip strength, 6-min walk test (6MWT), and timed chair stands) were collected. Long-term recovery was defined by reaching scores within the minimum clinically important difference of normative data. Global QOL recovery was seen in 79% at 1 year, 75% at 2 years, and 86% at 3 years. At 3 years, the QLQ-C30 subscales with the greatest recovery were physical and emotional functioning. For FACT-fatigue, recovery was seen in 68% at 1 year and 77% at 3 years. Recovery on PPMs was poorer on average, with only 17% on the 6MWT and 42% in grip strength returning to normal at 3 years. The vast majority of AML survivors after IC achieve recovery in QOL and fatigue by three years. However, recovery in physical performance remained blunted.

An evaluation of outpatient bone marrow harvesting.

In order to avoid the difficulties in scheduling and cost involved in admitting patients to hospital to undergo bone marrow harvests, we assessed outpatient marrow harvesting for autologous bone marrow transplant (BMT) candidates. Over a 13-month period, 39 consecutive patients with hematologic malignancies underwent bone marrow harvests as outpatients. For comparison we also evaluated 20 consecutive patients with similar disease status who had undergone bone marrow harvests as inpatients over the preceding 6 months. The mean hemoglobin value prior to harvest the mean volume of marrow harvested, and the mean nucleated cell count in the outpatient group were not significantly different from those of the inpatient group. There were no intraoperative complications. Of these 39 patients, 36 were discharged later the same day on oral iron supplements, with no adverse sequelae. Local pain was well controlled at home with mild oral analgesics. Two patients required admission due to postoperative hypotension--both responded promptly to intravenous (IV) fluids and blood and were discharged the following day. One patient was admitted postoperatively due to fever. There was a trend for the outpatients to receive less intra- and postoperative blood transfusions, but this did not reach statistical significance. The results suggest that most candidates for autologous BMT can safely undergo bone marrow harvesting as outpatients, thereby relieving pressure for hospital beds, potentially reducing costs and improving bed utilization. The study also raises the possibility of safely performing outpatient harvests on allogeneic BMT donors.

High-dose etoposide and melphalan, and autologous bone marrow transplantation for patients with advanced Hodgkin's disease: importance of disease status at transplant.

PURPOSE: To evaluate an intensive therapy regimen of high-dose etoposide and melphalan and autologous bone marrow transplantation (ABMT) in advanced Hodgkin's disease; and to determine possible prognostic factors that predict for long-term disease-free survival (DFS). PATIENTS AND METHODS: Seventy-three patients with advanced Hodgkin's disease who had failed to achieve remission with front-line chemotherapy (n = 16) or who had relapsed (n = 57) were treated with high-dose etoposide 60 mg/kg and melphalan 160 mg/m2 and ABMT. Previous therapy included mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) alternating with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), or hybrid MOPP/ABV. All patients received pretransplant cytoreduction with conventional-dose salvage chemotherapy and 40 also received pretransplant extended-field radiation to areas of bulky nodal disease (> 5 cm). RESULTS: Response to high-dose etoposide and melphalan was determined at 3 months post-ABMT. The complete response (CR) rate was 75% (95% confidence interval [CI], 64% to 84%), including 35 of 50 patients with measurable disease before ABMT (70%; 95% CI, 60% to 86%). There were three early deaths (septicemia) and four late deaths (three interstitial pneumonitis, one intracerebral hemorrhage). Actuarial DFS is 38.6% at 4 years. Multivariate regression analysis showed that disease status at the time of ABMT (no evidence of disease [NED], nonbulky residual disease [NBRD], or bulky disease) was the most important factor determining DFS: 68% of those transplanted with NED versus 26% for patients with NBRD and 0% for bulky disease (P = .0002, log-rank test). Relapse in a previous radiation field was the only other significant prognostic factor. CONCLUSION: Etoposide and melphalan is an effective and well-tolerated intensive therapy regimen in advanced Hodgkin's disease. Patients in complete remission after conventional-dose salvage therapy transplanted with this regimen enjoy superior long-term DFS.

Mini-BEAM as salvage therapy for relapsed or refractory Hodgkin's disease before intensive therapy and autologous bone marrow transplantation.

PURPOSE: To evaluate the efficacy of carmustine (BCNU), etoposide, cytarabine (Ara-C), and melphalan (mini-BEAM) as salvage therapy in patients with relapsed or refractory Hodgkin's disease who were potentially eligible to undergo intensive therapy and autologous bone marrow transplantation (ABMT). PATIENTS AND METHODS: Forty-four patients with refractory or relapsed Hodgkin's disease after front-line combination chemotherapy referred for consideration of ABMT were treated with mini-BEAM (BCNU 60 mg/m2 on day 1, etoposide 75 mg/m2 on days 2 to 5, Ara-C 100 mg/m2 twice per day on days 2 to 5, and melphalan 30 mg/m2 on day 6) to maximum response. Eleven patients were refractory to primary chemotherapy. Twenty-three patients were treated in first relapse and 10 in second or subsequent relapse; 21 received mini-BEAM as their first salvage regimen. Patients were restaged to determine disease status immediately before intensive therapy and transplant. RESULTS: The overall response rate was 84% (exact 95% confidence interval [CI], 70% to 92%), with a complete response (CR) rate of 32% (95% CI, 20% to 47%) and a partial response (PR) rate of 52%. No treatment-related deaths were observed. Myelosuppression was the major toxicity. Almost all patients required platelet transfusions. Eighty-four percent were given RBC transfusions, and 54% required intravenous antibiotics for fever while neutropenic. CONCLUSION: Mini-BEAM is a safe and effective regimen for treatment of refractory or relapsed Hodgkin's disease. Further studies are required to determine if responding patients have improved disease-free survival (DFS) after intensive therapy and ABMT.

Treatment of elderly patients with acute lymphoblastic leukemia--evidence for a benefit of imatinib in BCR-ABL positive patients.

All patients with acute lymphoblastic leukemia (ALL) over age 60 years seen at Princess Margaret Hospital over an 11-year period were analysed retrospectively. Of 53 patients, 45 received multiagent induction chemotherapy using a variety of regimens. There were 13 BCR-ABL positive patients, 9 of who received imatinib mesylate, either during induction or post-remission therapy. The overall complete remission (CR) rate of all 45-induction patients was 56%, with a 27% induction-related mortality rate. The CR rate was not influenced by induction regimen, age, initial WBC, LDH or BCR-ABL status. The median overall survival of the induction patients was 9 months, while the median progression-free survival (PFS) of the patients achieving CR was 10 months. The estimated overall survival (OS) at 3 years was 18.4% (95% CI: 9.8-34.3%). Age and initial WBC did not significantly predict for OS when evaluating the entire group of induction patients. However, there was a strong trend for BCR-ABL status to favorably predict for PFS, and for OS when only patients treated after July 2000 (when imatinib became available) were evaluated. The results indicate that ALL remains a poor prognosis disease in elderly patients, and that aggressive induction regimens designed for younger patients are very toxic for these patients. These data suggest that BCR-ABL+ ALL is becoming a relatively more favorable prognosis disease in the elderly, likely due to the influence of imatinib therapy. Further regimens should explore the use of less aggressive regimens in elderly patients and should evaluate the optimal way of combining imatinib with conventional agents in BCR-ABL+ patients.

Maintenance of Philadelphia-chromosome-positive progenitors in long-term marrow cultures from patients with advanced chronic myeloid leukemia.

We investigated the marrows of 19 patients with advanced Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in long-term marrow culture (LTMC) to determine the frequency of loss of clonogenic leukemic cells in vitro. Sixteen patients were in first chronic phase at a median of 24 months from diagnosis and had received prior therapy with busulphan and/or hydroxyurea. The effect of interferon therapy on loss of Ph+ clonogenic cells in LTMC was also investigated. Of 16 patients who had not previously received interferon, complete loss of Ph+ progenitors was documented by 4-5 weeks in the LTMCs from two (12.5%). Ph+ progenitors persisted at 4-5 weeks in the LTMC derived from 12 patients. Marrows from nine patients treated with interferon were also established in LTMC. Cultures from four patients did not yield colonies with detectable metaphases at 3-5 weeks, while Ph+ clones were present in the cultures initiated with marrows from five patients. Mean hematopoietic colony yields from the adherent layer at 2-4 weeks, and from the supernatant layer at 1-3 weeks, of cultures derived from interferon-treated patients were significantly lower than in LTMCs of patients not treated with interferon (p less than 0.05). The results indicate that in previously treated patients with late chronic phase CML there is a low frequency of conversion of Ph-negative hematopoiesis in long-term culture. Interferon therapy is associated with impaired progenitor yields in LTMC and does not improve selective loss of Ph+ progenitors.

Interleukin-3 followed by GM-CSF for delayed engraftment after autologous bone marrow transplantation.

Recombinant human interleukin-3 (IL-3) is well-tolerated according to phase I studies, and produces trilineage hematologic responses in patients with normal bone marrow. In addition, promising results have been obtained in a variety of bone marrow failure states. We studied IL-3 in 7 patients with markedly delayed engraftment after autologous bone marrow transplantation (ABMT) for hematologic malignancies (acute myeloid leukemia 4, chronic myeloid leukemia 1, myeloma 1, non-Hodgkin's lymphoma 1). All patients were red blood cell- and platelet transfusion-dependent, had an absolute neutrophil count (ANC) < 0.7 x 10(9)/L and failed to achieve a sustained ANC > 1.0 x 10(9)/L after receiving granulocyte-macrophage colony stimulating factor (GM-CSF) for 28 days. IL-3 was given daily for 21 days at 2 micrograms/kg/d (2 patients) and 5 micrograms/kg/d (5 patients). Toxicity was mild and consisted mostly of low-grade fever and malaise. No changes in platelet, hemoglobin or reticulocyte levels were observed. Four patients had at least a 2-fold increase in ANC at the end of IL-3 treatment. Five patients received GM-CSF 10 micrograms/kg/d subcutaneously for 7 to 10 days immediately after IL-3 and 4 had a further increase in ANC (median 1.7-fold, range 1.6- to 5.8-fold), but no change in platelet transfusion requirements. Hematopoietic colony assays of bone marrow cells obtained before and after treatment showed that granulocyte-macrophage colony-forming cell (CFU-GM) and erythroid blast-forming cell (BFU-E) levels were severely reduced and multilineage progenitors (CFU-GEMM) absent in all patients, and remained low after IL-3 treatment for 21 days. Sequential IL-3 and GM-CSF produced a significant but transient increase in the neutrophil counts of some patients. IL-3 appears to be of limited benefit in patients who are severely aplastic after ABMT and have very low levels of bone marrow progenitors.

GM-CSF therapy for delayed engraftment after autologous bone marrow transplantation.

Based on previous observations that granulocyte-macrophage colony-stimulating factor (GM-CSF) promotes granulocyte recovery following chemotherapy, we evaluated the effect of recombinant human GM-CSF on hematopoietic progenitors and clinical outcome in six patients with delayed engraftment (greater than 55 days) after high-dose therapy and autologous bone marrow transplantation (ABMT). Three patients responded to a 14-day course of GM-CSF (10 micrograms/kg body weight/day) with at least a sevenfold rise in circulating granulocytes and a corresponding increase in granulopoietic activity in the bone marrow. A fourth patient died of infection on the 8th day of GM-CSF therapy with no evidence of response, and the remaining two, one of whom received a lower dose of GM-CSF (5 micrograms/kg/day), did not respond. There was no change in platelet or red cell transfusion requirements in any patient during the treatment. In two of the three responders, the granulocyte counts returned to pretreatment levels by 4 and 7 weeks after stopping the drug, respectively. We observed a marked increase in marrow-derived as well as in circulating granulocyte-macrophage progenitors (granulocyte-macrophage colony-forming units, CFU-GM) by the end of the 14-day course of GM-CSF in the three responders. There was no change in the frequency of circulating or marrow-derived erythroid (erythroid burst-forming units, BFU-E) or multilineage (multilineage colony-forming units, CFU-GEMM) progenitors. The results indicate that GM-CSF therapy in patients with markedly delayed engraftment after ABMT may stimulate granulopoiesis, but the effect is transient in some patients.

A phase II exercise randomized controlled trial for patients with acute myeloid leukemia undergoing induction chemotherapy.

Curative treatment for acute myeloid leukemia (AML) involves induction chemotherapy (IC) which is associated with bed rest and toxicities, leading to worsening quality of life (QOL), fatigue, and fitness. Exercise during IC may ameliorate declines but has not been rigorously tested. We examined the efficacy of supervised exercise during IC on QOL, fatigue, and fitness. Eighty-three inpatients age 18-80 scheduled to receive IC for newly diagnosed or relapsed AML were randomized 2:1 (exercise intervention:control group). Study measures were completed at baseline, post-IC, and following the first cycle of consolidation. The intervention consisted of a supervised mixed-modality, moderate-intensity exercise program (4-5 days per week, 30-60min per session) throughout admission. Recruitment was good (56%), retention excellent (96%), and adherence was 54%. Global QOL improved similarly in both groups from baseline to post-IC (between-group difference 3.0 points, p=0.62). Fatigue improved in the exercise group from baseline to post-IC (potentially clinically important between-group difference of 3.6 points, p=0.23). Aerobic fitness, lower body strength, and grip strength improved in the exercise group (between-group differences p=0.005, p<0.001, p=0.03, respectively). Supervised exercise for patients with AML undergoing IC is feasible, safe, and appears effective at improving fitness and possibly fatigue. A larger trial is warranted.

Effect of antimicrobial prophylaxis on hematopoietic recovery following autologous bone marrow transplantation: ciprofloxacin versus co-trimoxazole.

We evaluated the effect of oral ciprofloxacin on neutrophil recovery in 20 consecutive patients undergoing autologous bone marrow transplantation (BMT) for malignant lymphoma and compared the results with a control group of 20 patients receiving co-trimoxazole and folinic acid. Both groups started the prophylactic antibiotic as well as granulocyte-macrophage colony-stimulating factor (GM-CSF) the day after marrow infusion and continued the former until the onset of febrile neutropenia (median duration of treatment 6 days for co-trimoxazole and 7 days for ciprofloxacin). The time of attain an absolute neutrophil count > or = 0.5 x 10(9)/L was significantly shorter in patients receiving ciprofloxacin (16 days vs 22 days; P = 0.006). There was no difference in time to attain a platelet count > or = 20 x 10(9)/L independent of transfusion or in time to the first febrile episode or incidence of bacteremia. We conclude that antibiotic prophylaxis with ciprofloxacin results in more rapid neutrophil recovery than prophylaxis with co-trimoxazole. This may result from a myelosuppressive effect of co-trimoxazole or an enhancement of neutrophil recovery by ciprofloxacin, or both.

Influence of total body irradiation on infections after autologous bone marrow transplantation.

Infectious complications were analysed in 50 consecutive autologous bone marrow transplant (ABMT) patients treated with high dose etoposide and melphalan, 30 of whom also received total body irradiation (TBI). Fever developed in 44 patients and bacteremia was documented in 13 (26%). Patients given TBI had increased susceptibility to bacteremia; 11 of 30 patients who received TBI had positive blood cultures, in contrast to two of the 20 who did not (p = 0.035). In addition, patients who received TBI had significantly more severe diarrhea (p = 0.037) when compared with those who received chemotherapy alone. Thirty-five patients treated with trimethoprim-sulfamethoxazole prophylaxis had a signficantly lower incidence of gram-negative bacteremia (p = 0.024). However, when those patients who received trimethoprim-sulfamethoxazole until neutrophil recovery were analysed alone, those who were also given TBI still had significantly more bacteremia (p = 0.047). Forty-seven patients with follow-up of more than 12 months are available for analysis of varicella zoster (VZV) infections. Of the 29 patients who received TBI, 11 (38%) developed VZV infections, in contrast to one of 18 patients (6%) treated with chemotherapy alone (p = 0.013). These results suggest that addition of TBI to the intensive therapy regimen for ABMT is associated with significantly more bacteremia and late VZV infections.

Acute transient parotitis after high dose etoposide and autologous bone marrow transplantation.

Etoposide is an important component of several intensive therapy regimens in allogeneic and autologous bone marrow transplantation for advanced hematologic malignancies. We observed the occurrence of transient acute parotid and submandibular sialoadenitis in nine of 19 patients receiving high dose etoposide and melphalan followed by autologous bone marrow rescue. Manifestations included pain, tenderness and swelling of the parotid and submandibular glands. Symptoms arose 4-16 h after completion of etoposide infusion and resolved within 72 h. Elevation of serum amylase accompanied the symptoms, and was also observed in some patients who were asymptomatic. Discomfort was controlled with analgesics and the clinical course was uncomplicated in all cases. Transient parotitis is a relatively frequent and benign complication of high dose etoposide therapy.

Analysis of factors affecting hematopoietic recovery after autologous bone marrow transplantation for lymphoma.

Thirty patients with relapsed lymphoma (14 Hodgkin's disease, 16 non-Hodgkin's lymphoma) who underwent autologous bone marrow transplantation (ABMT) were assessed for the effect of different parameters on the rate of hematologic recovery post-ABMT. There was no correlation between nucleated cells count or numbers of CFU-GM or BFU-E in the infused marrow on either neutrophil or platelet recovery times. Patients with lymphoma who received more salvage chemotherapy (greater than six cycles) prior to marrow harvest took significantly longer to recover neutrophils to greater than 0.5 x 10(9)/l (p = 0.0229) and platelets to greater than 20 x 10(9)/l (p = 0.0007) than patients who received less than five cycles of salvage chemotherapy prior to harvest. There was no significant correlation between underlying disease, use of total body irradiation or status of cytomegalovirus serology and recovery times post-ABMT. The results suggest that extensive salvage chemotherapy may result in considerable stem cell damage to marrow, and that potential ABMT candidates with lymphoma should undergo harvest of tumor-free bone marrow as soon as possible following first relapse.

Evaluation of cytoreductive therapy prior to high dose treatment with autologous bone marrow transplantation in relapsed and refractory Hodgkin's disease.

Based on observations that bulky disease at autologous bone marrow transplantation (ABMT) may be correlated with poor outcome in Hodgkin's disease, we have assessed the ability of conventional-dose chemoradiotherapy to reduce tumour burden to a minimum prior to ABMT. Thirty-seven patients with relapsed or refractory Hodgkin's disease referred for intensive therapy and ABMT were treated initially with one to five cycles of DHAP chemotherapy. All patients had previously received MOPP and ABVD chemotherapy or similar regimens. Four patients achieved complete remission (CR) and 12 partial remission (PR), for a total response rate of 43%. Eight partial responders and four non-responders to DHAP achieved significant further tumour reduction with local radiotherapy (five CR, seven PR). Six of 10 non-responders to DHAP responded to alternative salvage chemotherapy (mini-BEAM, CEP or augmented CVP). Overall, 24/37 patients (65%) achieved effective cytoreduction (nine CR, 15 PR with minimal disease) and have proceeded to ABMT. Patients with bulky disease at relapse or limited stage (II, IIIA) at diagnosis were less likely to respond to DHAP, but some of these could be cytoreduced with alternative therapy. In addition, the number of prior chemotherapy regimens correlated inversely with likelihood of response to DHAP. The results indicate that approximately two-thirds of patients with Hodgkin's disease who relapse after MOPP and ABVD-like regimens can achieve effective cytoreduction with conventional-dose chemoradiotherapy and proceed to ABMT in CR or PR with minimal disease.

The role of allogeneic bone marrow transplantation in adult patients below the age of 55 years with acute lymphoblastic leukemia in first complete remission: a donor vs no donor comparison.

The role of allogeneic bone marrow transplantation (alloBMT) in adults with acute lymphoblastic leukemia (ALL) in first complete remission (CR1) remains controversial. At our institution, the policy is to offer alloBMT to ALL patients in CR1 up to the age of 55 years if a related donor is available. In addition, unrelated donor transplants are offered to patients with Philadelphia (Ph+) ALL. We report the results on 92 patients with ALL treated according to this policy from September 1992 to October 2001. Of the 87 patients achieving CR1, the comparison of patients with (n=48) or without donors (n=39) was done using an intention-to-treat approach. Of the 48 patients with donors (39 related and nine unrelated), 35 (73%) received alloBMT in CR1. No significant difference in 3-year event-free survival (EFS) (40 vs 39%, P=0.74) or overall survival (OS) (46 vs 58%, P=0.41) was seen in 'donor' vs 'no-donor' groups. For Ph+ patients, 3-year EFS and OS in 'donor' group were 46 and 57%, respectively, none of the patients in 'no-donor' group survived beyond 3 years. With our treatment strategy, 3-year OS of Ph+ patients was equivalent to Ph-negative (Ph-) patients (51 vs 52%, P=0.77). In conclusion, our data show that the policy of performing alloBMT if a sibling donor is available has not resulted in better outcome in Ph- patients.

A regional autologous bone marrow transplant network: transfers to designated centers on the day after transplant.

Autologous bone marrow transplantation (ABMT) is becoming increasingly prevalent for treatment of advanced malignant disease. In order to increase the availability and utility of this therapy, we assessed the feasibility of transferring patients to their regional referral centers on the day after marrow infusion (day 1), for management post-transplant. This prospective study compares the outcome of 77 patients either transferred the day after marrow transplant for subsequent management at one of six selected Canadian regional centers closest to their domicile, or treated entirely at The Toronto Hospital, according to a common protocol. Study end-points included frequency of complications during transfer, transplant-related morbidity and mortality and hematopoietic recovery. Assessment of eligibility for transplant, bone marrow harvesting, autograft cryopreservation, administration of intensive therapy and marrow infusion were conducted in all cases at The Toronto Hospital. Thirty patients received marrow transplants and were transferred on day 1. There were no complications during transfer. Compared with 47 consecutive patients treated entirely at The Toronto Hospital, there were no differences in treatment-related morbidity or mortality, use of intravenous antifungal therapy or total days of hospitalization. We conclude that day 1 transfer of patients after ABMT to designated centers is feasible and safe. The operation of a regional ABMT network appears to benefit patients, relatives, referring physicians, the transplant center and may also improve health care delivery.

Spontaneous acute tumor lysis syndrome in acute myeloid leukemia? A single case report with discussion of the literature.

Acute tumor lysis syndrome (ATLS), a condition which results from a rapid destruction of tumor cells with massive release of cellular breakdown products, has been well described following the treatment of various malignancies. However, only a handful of cases of spontaneous ATLS have been reported in the literature. We describe the first reported case of spontaneous ATLS in acute myeloid leukemia (AML). A previously healthy 63 year old woman presented with a two month history of fatigue and a one week history of easy bruising. On admission she had oliguric acute renal failure, with marked elevation in serum uric acid and phosphate. A bone marrow biopsy showed AML M7 with fibrosis. The renal failure resolved with supportive care and institution of allopurinol therapy. Following this, AML induction chemotherapy resulted in complete remission. Her biochemical and clinical course were very similar to the classical ATLS seen in patients after chemotherapy. Therefore, this case represents a rare instance of acute renal failure from spontaneous ATLS, and in our opinion the first reported occurrence of spontaneous ATLS associated with AML.