Background Although induction chemotherapy results in remission in many older patients with acute myeloid leukemia (AML), relapse is common and overall survival is poor. Methods We conduct...

https://www.nejm.org/doi/suppl/10.1056/NEJMoa2004444/suppl_file/nejmoa2004444_appendix.pdf

Oral Azacitidine Maintenance Therapy for Acute Myeloid Leukemia in First Remission.

We studied the incidence among, risk factors for, and survival of adult patients with acute leukemia and hepatosplenic candidiasis during the period 1980 to 1993. Of 562 adult patients with acute leukemia, 38 (6.8%) had hepatosplenic candidiasis. The incidence of infection increased fivefold during the study period. The incidence was higher among patients with acute lymphatic leukemia (11.3%) than among those with acute myeloid leukemia (5.1%) (P = .01). The median survival was 9.5 months, and by the end of follow-up, 74% of patients had died. Patients whose leukemia was in remission before the last cytotoxic treatment preceding hepatosplenic candidiasis survived longer than did patients with newly diagnosed or refractory or relapsed leukemia (P = .0065). Eleven patients died within 3 months after the diagnosis of the infection: 7 of 16 with newly diagnosed leukemia, 4 of 10 with refractory or relapsed leukemia, and 0 of 12 with leukemia in remission (P = .028). In all of the patients who died within 3 months, infection was found at autopsy. In conclusion, the incidence of hepatosplenic candidiasis has significantly increased since 1980, and the outcome for patients with this infection is related to the stage of leukemia.

Hepatosplenic candidiasis in patients with acute leukemia : Incidence and prognostic implications

The diagnosis of multiple myeloma (MM) is often difficult; most patients present with asymptomatic gammopathy. The only findings that confirm a diagnosis of MM are an elevation in the M-component or extension of the lytic bone lesions that are the hallmark of the disease. Tests that delineate plasma cell biology, such as plasma cell proliferation rate, are helpful; magnetic resonance imaging can disclose bone marrow lesions leading to subsequent osteolytic disease. After the diagnosis of MM has been established and prognostic factors identified, the appropriate therapy can be determined. Melphalan and prednisone are no longer considered to be the "gold standard" of therapy. In fact, this approach is suitable for less than half of patients with myeloma. This article presents guidelines for standard treatment options and examines the efficacy of new high-dose chemotherapy approaches.

https://www.hemonc.theclinics.com/article/S0889-8588(05)70418-4/pdf

Diagnosis, prognosis, and standard treatment of multiple myeloma

Curative treatment in acute myeloid leukemia (AML) depends on successful induction therapy to achieve a complete remission (CR), and subsequent post-remission therapy to prevent relapse. High relapse rates after consolidation therapy and after allogeneic stem cell transplant contribute to suboptimal outcomes in AML patients, and continue to represent a difficult challenge. Effective maintenance therapy could play an important role in prolonging the remission interval in the post-consolidation setting, especially in high risk AML patients. Maintenance treatment approaches based on conventional chemotherapy, immunotherapy, hypomethylating agents, and targeted small molecules have been explored in this setting, but no data so far have been convincing enough to establish this approach as the standard of care. However, ongoing and future studies including novel targeted therapies may demonstrate promising efficacy that could facilitate incorporation of maintenance therapy into clinical practice. In this review we summarize previous and ongoing approaches of maintenance therapy in AML and discuss the most promising strategies.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/ajh.25620

Maintenance therapy in AML: The past, the present and the future.

PURPOSETo study the toxicity and potential efficacy of busulfan (BU) and cyclophosphamide (CY) as a conditioning regimen before allogeneic bone marrow transplantation (ABMT) in patients with multiple myeloma (MM).PATIENTS AND METHODSTwenty patients with MM underwent conditioning, which was followed by ABMT from 16 HLA-identical donors, three one-antigen-mismatched donors, and one HLA A, B, D-identical unrelated donor. Four levels of BU plus CY were evaluated.RESULTSSevere regimen-related toxicity occurred in two of five patients who received BU 16 mg/kg and CY 120 mg/kg, in none of the four patients who received BU 14 mg/kg and CY 120 mg/kg, in one of eight patients who received BU 14 mg/kg and CY 147 mg/kg, and in two of three patients who received BU 14 mg/kg and CY 174 mg/kg. Twelve of 15 (80%) assessable patients achieved a complete remission with the disappearance of M-protein and the return of normal marrow morphology. Ten patients died of complications related to the ABMT, and two patients died of ...

Phase I study of busulfan and cyclophosphamide in preparation for allogeneic marrow transplant for patients with multiple myeloma.

108 consecutive patients with de novo acute myeloid leukaemia at ages 15 to 59 years were treated in a prospective controlled multicentre trial. Induction with combination TAD resulted in a complete remission in 85 cases (79%). After a cyclic consolidation programme for 6 months, 73% of the remissions continued. The maintenance therapy was at random either nothing, or alpha interferon, or monthly 5 day courses with thioguanine and cytarabine. The median duration of all remissions was 13 months; that of those in the control and interferon arms 15 months each, and in the chemotherapy arm 18 months. The median survival of all the 108 patients was 16 months; that of those in the control arm 20 months, in the interferon arm 33 months and in the chemotherapy arm 26 months. At 5 yr, 31%, 22% and 31%, respectively, were alive. The survival curves did not differ from each other significantly. Maintenance treatment after an intensive induction and a moderately intensive consolidation was of no benefit in this study. Interferon did not improve the prognosis.

Value of maintenance therapy with chemotherapy or interferon during remission of acute myeloid leukaemia.

In a randomised multicentre trial a combination of methylprednisolone, vincristine, CCNU, cyclophosphamide and melphalan (MOCCA) was compared with intermittent melphalan and prednisone (MP) as primary treatment in multiple myeloma. In the MP arm the refractory or relapsed patients were treated with regimen MOCCA. The MOCCA arm produced a response rate of 75% among 64 patients and the MP arm a response rate of 54% among 66 patients. The median survival was 41 months in the MOCCA arm and 45 months in the patients primarily randomised to the MP arm. The initial response to MOCCA improved the survival, while this effect was not statistically significant in the MP arm. The results show that the median survival does not increase if aggressive chemotherapy is employed as the first line treatment in multiple myeloma.

Treatment of multiple myeloma with an intensive 5-drug combination or intermittent melphalan and prednisone; a randomised multicentre trial

Patients aged 70 yr or older with multiple myeloma were treated, when suitable, according to concurrent trial protocols for younger patients, with the exception that the cytostatic regimen was not allocated at random. Intermittent melphalan and prednisone (MP) was given as the primary treatment to 42 patients and 5-drug combination MOCCA to 68 patients. The groups were comparable with each other, and the distribution of the clinical stages of the patients was similar to the younger patients in concurrent trials. An at least 50% response was achieved in 33% (SE 7.3) with MP and in 75% (SE 5.3) with MOCCA. The median survival times were 39 and 32 months, the relative age-adjusted survival times 45 and 41 months, respectively. Advanced age as such is thus no contraindication for active treatment of myeloma, and in suitable patients the results compare well with those achieved in younger patients.

Treatment of multiple myeloma in old patients

In a randomised multicentre trial a combination of methylprednisolone, vincristine, lomustine, cyclophosphamide and melphalan (MOCCA) was compared with the same regimen omitting methylprednisolone after the first course (COLA) in previously untreated patients with multiple myeloma. The MOCCA arm showed a response rate of 72% among 79 patients and the COLA arm a response rate of 60% among 59 patients. This difference was not statistically significant. The median survival time was 56 months in the MOCCA arm and 61 months in the COLA arm. There was a slight increase of early deaths (within the first 6 months) in the MOCCA arm as compared with the COLA arm. We conclude that, in multidrug therapies, the continuation of corticosteroid at conventional dosage beyond the first course does not improve response rate or survival time in multiple myeloma.

Corticosteroid is not beneficial in multiple-drug combination chemotherapy for multiple myeloma

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Value of maintenance therapy with chemotherapy or interferon during remission of acute myeloid leukaemia.

Treatment of multiple myeloma with an intensive 5-drug combination or intermittent melphalan and prednisone; a randomised multicentre trial

Treatment of multiple myeloma in old patients

Corticosteroid is not beneficial in multiple-drug combination chemotherapy for multiple myeloma