Low Dose Melphalan and Bortezomib for AML and High-Risk MDS

Inclusion Criteria: * Pathologic diagnosis of AML or high-risk MDS Patients with chronic myelomonocytic leukemia or a refractory cytopenia with multilineage dysplasia are eligible if that have one of the following criteria: * \>4 units of red blood cells transfused during the previous 3 months * platelet count \<50,000/uL * absolute neutrophil count \<1000/uL and a recent infection requiring antibiotics * Patients may either be considered to be poor candidates for standard induction chemotherapy based on reasonable medical evidence or have declined such therapy, but still desire palliative treatment beyond that of best supportive care * Primary refractory disease or have disease that has relapsed after prior cytoxic therapy * Karnofsky performance status of \>50% * Patients may receive prior growth factor therapy * Patients who received prior therapies (ex. melphalan, 5-azacitidine, low-dose cytarabine) to control their MDS or AML prior to registration (Stratum 2), but are clearly nonresponders are eligible for enrollment if expected toxicity of the prior therapy has resolved * Voluntary written informed consent * If female, the subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (ie, a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study * If male, the subject agrees to use an acceptable method for contraception for the duration of the study * Patients that have been previously treated will be eligible for study if: 1. the previous therapy was ineffective and 2. all expected toxicity of the previous treatment has resolved 3. In general the following guidelines regarding the elapsed time from previous treatment to eligibility should be followed 1. High intensity cytotoxic treatment (7\&3 induction, High Dose Ara-C): 4 weeks 2. Hematopoeitic growth factors: no delay required 3. Low intensity treatment (such as oral melphalan or hydrea, low dose cytarabine or 5-azacitidine) No delay required if expected toxicity has resolved and regimen ineffective Exclusion Criteria: * AML FAB M3 * No concomitant malignancy other than a curatively treated carcinoma in situ of cervix or basal or squamous cell carcinoma of the skin * Active, uncontrolled infections * Chronic liver disease not due to AML, or bilirubin \>2.0mg/dL * End stage kidney disease on dialysis * Active CNS disease. A lumbar puncture prior to treatment is not required and should not be performed in the absence of significant CNS symptoms or signs * Patient has sensory peripheral neuropathy \> grade 2 or painful peripheral neuropathy \> grade 1 (see appendix A for NCI sensory neuropathy toxicity criteria) within 14 days before enrollment * Hypersensitivity to bortezomib, boron or mannitol * Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum B-human chorionic gonadotropin (B-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women * Serious medical or psychiatric illness likely to interfere with participation in this clinical study