Autologous bone marrow transplantation for high-grade lymphoid malignancy using melphalan/irradiation conditioning without marrow purging or cryopreservation. The Northern Regional Bone Marrow Transplant Group

Abstract

We report the safety and efficacy of 34 consecutive autologous bone marrow transplant (ABMT) procedures performed in adult patients with high-grade lymphoid malignancy after remission induction therapy. Fifteen patients with acute lymphoblastic leukemia (ALL) and six with high-grade non-Hodgkin's lymphoma (NHL) received pretransplant conditioning with intravenous (IV) melphalan and fractionated total body irradiation (TBI). Thirteen other patients with NHL were conditioned with melphalan alone, having previously received local involved field radiotherapy. Unmanipulated noncryopreserved autologous marrow was reinfused within 48 hours of harvesting. Engraftment occurred in all patients with medians of 10 days of neutropenia (neutrophils less than 0.5 x 10(9)/L), 4-day platelet transfusion requirement, 3 U packed RBC transfusion, and 18 days in hospital posttransplant. There were no procedure-related deaths. Actuarial disease-free survival in the 13 patients with ALL receiving autotransplant early in first remission is 48% with a median follow-up of 3 years. Two other ALL patients who had autotransplants after a period of maintenance therapy also remain in complete remission (CR). These results compare favorably with our 34% disease-free survival (DFS) in 15 allogeneic ALL transplant patients and 21% DFS in 19 patients on standard maintenance after a common induction schedule. No relapses have occurred in the 17 NHL patients transplanted in remission (median follow-up 2 years), but the two NHL patients who developed recurrent disease before ABMT died of progressive disease after temporary responses. We conclude that this method of ABMT results in rapid reengraftment with lack of toxicity and that the conditioning treatment used shows good efficacy against disease. It is applicable in high-grade lymphoid malignancy in first remission, and our results call into question the need for marrow purging in ALL and NHL patients transplanted in first remission.

Non-cryopreserved peripheral blood stem cells autotransplants for hematological malignancies can be performed entirely on an outpatient basis

“…Efforts to make the benefits of hematopoietic stem cell transplants acquaintable to a larger number of patients have been manifold [5-6, 9-11, 19]. Grafting PBSC instead of bone marrow stem cells has been shown to be less costly [20]; on the other hand we [4,5] and others [21][22][23][24][25] have shown that autografts can be performed safely without freezing devices, keeping the stem cells in a conventional blood bank refrigerator, at 4°C, for up to 96 hr. It has also been shown that stem cells can be frozen without controlled cryopreservation [26], that hematopoiesis can be restored using mobilized whole unprocessed blood [27], and that a single, large volume apheresis procedure could be enough to obtain apheresis products capable to reconstitute hematopoiesis after ablative chemotherapy [26].…”

Long‐term storage of peripheral blood stem cells frozen and stored with a conventional liquid nitrogen technique compared with cells frozen and stored in a mechanical freezer

“…C onventional methods of cryopreservation of hematopoietic stem cells (HSCs) obtained from marrow or peripheral blood involve controlled-rate freezing using 10% dimethyl sulfoxide (DMSO) as the cryoprotectant and storage of the cells in liquid nitrogen. [1][2][3][4][5][6] Although the 10% DMSO method is cumbersome and requires complex equipment, it began to be used clinically for both autologous [7][8][9][10][11] and later allogeneic 12 human transplantation. Thus, cryopreservation using only DMSO has become standard involving 10% final concentration, controlled-rate freezing, and subsequent storage in liquid nitrogen.…”

Worldwide Network for Blood and Marrow Transplantation Recommendations for Establishing a Hematopoietic Stem Cell Transplantation Program in Countries with Limited Resources, Part II: Clinical, Technical, and Socioeconomic Considerations

“…These autologous transplantation techniques were reported to yield early engraftment and reduced hospital length of stay, with significant cost savings. Outcomes were comparable to those from conventional conditioning with cryopreserved stem cells in patients with multiple myeloma [31][32][33][34]. Two recent studies of noncryopreserved autografts from developing countries using post-HSCT G-CSF also indicate comparable engraftment rates to cryopreserved autografts [35,36].…”

“…Several centers have recently reported outcomes of autologous HSCT for multiple myeloma using noncryopreserved stem cells without G-CSF support [31][32][33][34]. The success of this technique depends on abbreviated conditioning, with 1 day of high-dose melphalan for patients with multiple myeloma and short-duration conditioning for patients with lymphoma.…”