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Background: Allografting induces long-term molecular remissions and possibly cure in myeloma patients. The development of non-myeloablative conditionings has reduced the transplant-related mortality (TRM) associated with myeloablation and extended the eligible age for transplantation. Moreover, high response rates are reported especially when allografting is preceded by cytoreductive high-dose chemotherapy. We investigated the feasibility of unrelated donor non-myeloablative transplantation as either part of the initial treatment plan or as salvage treatment in heavily pretreated patients., Methods: Twenty-two patients underwent non-myeloablative allografting, 10 as part of their initial treatment and 12 at relapse. Donors were matched for HLA-A, B, C, DRB1 and DQB1 by high-resolution typing. Only one single class I allele disparity was allowed. Conditioning consisted of fludarabine 90 mg/m(2) and 2 Gy total body irradiation. Graft-vs.-host disease (GVHD) prophylaxis included cyclosporin and mycophenolate mofetil., Results: All patients except two (91%) readily engrafted. After a median follow-up of 20 (10-30) months, incidences of grade II-IV acute and extensive chronic GVHD were 50% and 61%. Overall response (OR) was 55%, with four (20%) complete and seven (35%) partial remissions. However, in patients allografted up-front OR was 89% whereas in the heavily pretreated group OR was 27% (P = 0.01). Two-year overall and event-free survivals were both 79% in the group transplanted up-front and 27% and 25% among relapsed patients (P = 0.025 and P = 0.006, respectively). Overall, six patients died of TRM and three of disease progression., Conclusions: Unrelated donor non-myeloablative allografting is feasible in myeloma. Disease control appears more pronounced when patients are treated soon after diagnosis.

Experimental and clinical data suggest that Ph-negative myeloid progenitor cells are present, albeit suppressed, in the bone marrow of chronic myeloid leukemia (CML) patients. These residual Ph-negative cells might, in certain circumstances, regain their proliferative advantage over the leukemic Ph-positive clone. Treating CML patients with intensive chemotherapy might allow the harvest, in the early phase of recovery, of Ph-negative stem cells to be used as graft after myeloablative regimen. In our study, 6 CML patients were admitted to a program of autograft with circulating stem cells (CSC) collected after high-dose (5 or 7 g/m2) cyclophosphamide (HD-CY) mobilization. All were autografted, using busulphan 16 mg/kg and melphalan 60 mg/m2. As graft, 4 patients received CSC only, while 2 patients were also given bone marrow, as their peripheral blood CFU-GM yield was unsatisfactory. Two previously alpha-IFN-responding patients showed a slow hematologic recovery, but achieved a marked and further reduction of their Ph-positive metaphases post-graft. Moreover, in one of them, cytogenetic analyses performed on apheresis product showed a more pronounced reduction of his Ph-positive metaphases, as compared to bone marrow samples, suggesting a potential purging effect of the mobilization procedure.

A 53-yr.-old woman with amyloidosis AL was treated with high-dose chemotherapy and autologous stem cell infusion in an attempt to suppress the amyloid secretion. A diagnosis of MGUS had been made six years earlier. During the last year her disease had progressively shifted to a full-blown picture of amyloidosis AL, with renal failure, proteinuria, renal amyloid deposition and plasma cell sheets in the marrow. After an unsuccessful attempt with standard-dose chemotherapy, she received a high-dose regimen of busulphan (14 mg/Kg) and melphalan (40 mg/m2), followed by the infusion of both autologous bone marrow and peripheral blood stem cells. She had full and prompt engraftment, but eight weeks post-graft developed interstitial pneumonitis: CMV was isolated. The patient died while in the intensive care unit. In the literature, this is the first case of amyloidosis AL treated with high-dose therapy and autologous transplantation.

A case of localized Trichosporon beigelii infection is reported in a 40-year-old woman with Ph+ chronic granulocyte leukemia who underwent autologous blood stem cell transplantation. On day +14 after autograft, while severely neutropenic, she developed a local infection involving the soft tissues surrounding the central venous catheter (CVC) point of entry into the subclavian vein. Trichosporon beigelii was isolated from culture of the CVC tip; resolution occurred after removal of the CVC, neutrophil recovery and antifungal treatment with amphotericin B and 5-fluorocytosine. To our knowledge this is the first case of CVC localized infection from Trichosporon beigelii after transplantation.

Circulating stem cells (CSC) are well documented in animals and humans. Though their function in normal conditions remains obscure, autologous CSC seem capable of restoring hemopoiesis after myeloablative treatment. With cell separators CSC may be harvested in adequate number, and collection may be further improved giving chemotherapy and/or GM-CSF that mobilize stem cells into the circulation. Due to the high number of progenitor cells infused, hematologic reconstitution is more rapid with CSC than with marrow cells. Autologous blood stem cell transplantation (ABSCT) is increasingly employed in a variety of hematologic malignancies and in some solid tumors. CSC allow transplantation in patients previously irradiated on the sites of harvest or with marrow tumor involvement, and probably decrease the risk of infection by shortening the duration of post-graft aplasia. Their use is also encouraged by a belief that, along with CSC, a large number of immunocompetent cells are infused that may exert an anti-tumor effect. A lower tumor contamination of CSC as compared to marrow is an attractive matter, but remains to be demonstrated. Standardization of cell cloning assays, identification of monoclonal antibodies to recognize the surface antigens expressed on progenitor cells, and definition of advantages of ABSCT are items of future work.

A 15-year-old boy with non-T ALL in early 2nd remission was autografted using a regimen with busulphan 4 mg/kg/day, po, from day -9 to -6, and cyclophosphamide 50 mg/kg/day, iv, from day -5 to -2. During busulphan administration he experienced a few generalized seizures, and starting on day 25 post ABMT he developed a progressively severe neurological symptomatology characterized by nystagmus, right VIth cranial nerve palsy, truncal ataxia and, finally, confusion and coma. MRI showed lesions in the periaqueductal gray matter, thalamus, mammillary bodies and putamen. Within 24 hours of treatment with thiamine he improved dramatically, but during the following weeks permanent neurologic damage with memory deficit, truncal ataxia and nystagmus became evident. To our knowledge this is the first case of Wernicke's encephalopathy reported after BMT. We suspect in this case a contribution of busulphan to the development of the syndrome.