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CD34+ cell dose calculations are usually based on actual body weight (ABW). We have shown that ideal body weight (IBW) may provide a better basis for this in a small population of patients with hematologic malignancies. This was studied further in 514 myeloma autografts. The CD34+ cell doses (106/kg) by IBW and ABW were 1.37–39.36 (median 6.03) and 1.15–29.67 (median 4.84), respectively. IBW-based cell doses correlated slightly better with engraftment than ABW-based doses (higher r2): 0.5 × 109/l neutrophils 0.83 versus 0.82, 1.0 × 109/l neutrophils 0.78 versus 0.77, 20 × 109/l platelets 0.54 versus 0.53 and 50 × 109/l platelets 0.57 versus 0.55. When outliers (hematologic recovery in <8 or >16 days) were excluded, the findings were similar: 0.5 × 109/l neutrophils 0.85 versus 0.84, 1.0 × 109/l neutrophils 0.85 versus 0.84, 20 × 109/l platelets 0.86 versus 0.85 and 50 × 109/l platelets 0.85 versus 0.84. CD34+ cell doses based on IBW as well as ABW significantly affected engraftment when analyzed separately as continuous variables. However, when analyzed together, only the dose based on IBW retained significance. We conclude that calculation of CD34+ cell numbers for autotransplantation should be based on IBW.Bone Marrow Transplantation (2009) 43, 301–305; doi:0.1038/bmt.2008.322; published online 6 October 2008 [ABSTRACT FROM AUTHOR]

Summary:The role of autologous stem cell transplantation in adult patients with acute myeloid leukaemia (AML) in first remission is unclear, yet it has become standard treatment for myeloma and this paper explores whether the source of transplanted stem cells may explain this paradox. In total, 57 patients from the Royal Marsden Hospital who received an unpurged bone marrow transplant (ABMT) were matched with 114 patients from the EBMT registry who had undergone peripheral blood stem cell transplantation (PBSCT). Patients were matched for karyotype, FAB type, remission-autograft interval and age. In the PBSCT group, haematopoietic recovery was significantly faster and nonrelapse mortality at 4 years was significantly lower (13 vs 1%, P=0.04). The relapse rate and overall survival at 4 years (20 vs 31% and 77 vs 63%) were also better with PBSCT, although the differences were not statistically significant. Autografting should be reassessed in a randomised trial for first remission AML patients using peripheral blood as a source of stem cells rather than bone marrow.Bone Marrow Transplantation (2004) 33, 1209-1214. doi:10.1038/sj.bmt.1704511 Published online 19 April 2004 [ABSTRACT FROM AUTHOR]

Summary:Growth factors are routinely used after autotransplantation to accelerate hematopoietic recovery, and are continued until the absolute neutrophil count (ANC) is ?0.5 × 109/l on 3 consecutive days. Since ANC often increases to very high levels with this strategy, we discontinued growth factor on the first day ANC reached 0.5 × 109/l in 45 patients (Study Group), and compared their subsequent ANC to 108 historic controls who received growth factor longer. While ANC on the day after reaching 0.5 × 109/l was comparable between groups, ANC on the third day was significantly higher in the Control Group (2.3 vs 4.9 × 109/l; P=0.0003). When compared to the first day, ANC in the Study Group was higher by a median of 140% on the third day and by 450% in the Control Group (P=0.0002). A significantly higher proportion of patients experienced a decline in ANC after the first day in the Study Group. However, only one patient in the Study Group became neutropenic transiently and ANC recovered spontaneously the next day. The incidence of fever and hospitalization were comparable. We conclude that growth factors can be discontinued after autotransplantation the day the ANC reaches 0.5 × 109/l, without compromising neutrophil recovery.Bone Marrow Transplantation (2004) 33, 715-719. doi:10.1038/sj.bmt.1704415 Published online 26 January 2004 [ABSTRACT FROM AUTHOR]

The time to myeloid recovery after autologous hematopoietic stem cell transplantation (HSCT) is usually defined as the first of 3 consecutive days with an absolute neutrophil count (ANC) of 0.5 × 109/l (ANC500). Universal documentation of ANC500 for 3 consecutive days, historically required to ensure robust myeloid recovery, has become difficult with a trend towards early discharge and outpatient HSCT. We studied 90 autografted patients to see how frequently ANC declined after having reached 0.5 × 109/l. ANC500 was documented on 2 and 3 consecutive days in 14 and 63 patients, respectively. ANC increased by a median of 213% from the 1st to the 2nd day (rise in 75 and unchanged in two), and by a median of 142% from the 2nd day to the 3rd (rise in 60, unchanged in one, and decline in two; higher than the 1st day in the latter three). The increase from the 1st to the 3rd day was 13–3433% (median, 557%). Thus, in all 63 patients, no decline below ANC500 was seen, and the first day with ANC500 was also the first of 3 consecutive days with ANC500. The remaining 13 patients had repeat counts 2–7 days after the 1st day with ANC500 documenting further increase in ANC with no evidence of failed engraftment. These data show that the first day with ANC500 is also consistently the first of 3 consecutive days with ANC500 in autografted patients. Therefore, the traditional definition of myeloid engraftment should be changed to consider the first day with ANC500 as the day of engraftment without necessarily documenting ANC500 on the subsequent 1–2 days. This simple change in definition has significant implications for how data are reported to transplant registries and how peer-review organizations such as the Foundation for the Accreditation of Hematopoietic Cell Therapy (FAHCT) define completeness of data.Bone Marrow Transplantation (2002) 30, 749–752. doi:10.1038/sj.bmt.1703741 [ABSTRACT FROM AUTHOR]

The role of more intense conditioning for second transplant was evaluated in myeloma patients achieving at least partial remission (PR) after first transplant with melphalan at 200 mg/m2. Forty-three patients received more intensive conditioning for the second transplant. Nineteen patients received cyclophosphamide 120 mg/kg along with melphalan 200 g/m2 (MEL-CY; group 1) while 24 patients received total body irradiation (1125 cGy) in conjunction with melphalan 140 mg/m2 (MEL-TBI; group 2). Forty-three matched control patients were identified from 450 patients receiving melphalan alone for second transplant (MEL200; group 3). Engraftment and toxicities were comparable among the groups with the exception of increased treatment-related mortality of 8% in group 2 compared to none in groups 1 and 3 (P = 0.07). Despite identical CR rates of 74, 71 and 70%, respectively, in groups 1, 2 and 3 (P = 1.0), event-free survival (median: 27, 15 and 61; P < 0.0001) and overall survival (median: 39, 25 and 76 months; P = 0.003) were significantly decreased in patients receiving more intensive conditioning (groups 1 and 2). Lymphocyte recovery, evaluated as a surrogate for immune recovery, was inferior in more intensively treated patients (groups 1 and 2 compared to group 3). Our findings suggest that more intense conditioning appears to have no benefit in patients responding to their first cycle of high-dose therapy and may even be detrimental in this setting. Bone Marrow Transplantation (2000) 25, 483–487. [ABSTRACT FROM AUTHOR]

Autologous stem cell transplantation after high-dose melphalan for the treatment with multiple myeloma has resulted in prolonged progression-free survival and overall survival in patients under 65 years. We have examined the role of autologous transplantation in 17 patients with multiple myeloma over 65 years at our centre using a matched pair analysis with younger patients. The median age of this cohort of patients over 65 years was 67 years (65–74) and their outcome and transplant-related morbidity was compared with 17 younger pair mates with a median age of 55 years (31–64). Sixteen patients received high-dose melphalan, and one received busulphan with autologous stem cell rescue. The high-dose therapy was well tolerated in both elderly patients and the matched pairs, with comparable time to recover neutrophils and platelets. Treatment-related mortality also did not differ significantly in both the groups. Median overall survival of the elderly patients was 3.59 years similar to 3.01 years of the pair mates (P = 0.92). Autologous stem cell transplantation after high-dose melphalan conditioning was equally well tolerated in groups of patients above and below 65 years. There was no difference in relapse rate, OS and myelotoxicity in both the groups. These findings suggest that advanced age should not be an exclusion criterion from autologous transplant programmes. Bone Marrow Transplantation (2000) 25, 533–539. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) has been reported as a cause of death among autologous peripheral blood stem cell (ASCT) and marrow recipients and recommendations for therapy with aerosolized ribavirin plus intravenous immunoglobulin (IVIG) made. This therapy is expensive, may be toxic, and causes a significant disruption of patient care. The purpose of this study was to evaluate the morbidity and mortality of RSV infections in patients with multiple myeloma undergoing ASCT without ribavirin therapy. During the months of February–April 1997, 10 consecutive patients (median age 57 years, seven males) with advanced and heavily pretreated myeloma underwent ASCT while having active RSV upper respiratory tract infection. After melphalan (200 mg/m2), all patients became neutropenic (<1000 cells/mm3) for a median of 7 days. Ribavirin was not given to any patient. No patient developed lower respiratory tract infection, required transfer to intensive care or died at a median follow-up of 8 months. One patient developed tracheobronchitis requiring oxygenation by nasal cannula. No delay in the treatment of the underlying myeloma was incurred. RSV infection may not necessarily be a contraindication for ASCT or an indication for therapy with aerosolized ribavirin. Additional studies are needed to confirm our preliminary findings. [ABSTRACT FROM AUTHOR]

Whereas patients with multiple myeloma continue to relapse after autologous transplantation and are unlikely to be cured, the probability of progression is less after allogeneic transplantation and a proportion of patients may be cured. This is attributable to an immunologically mediated graft-versus-myeloma (GVM) effect which is akin to the well-known graft-versus-leukemia effect. The available clinical and experimental evidence strongly support the existence of GVM, but it is not known whether GVM is separable from graft-versus-host disease (GVHD) in practice. The best way to exploit GVM reactions is unclear, and the morbidity and mortality associated with GVHD undermine long-term survival. There is usually a time lag of a few weeks between immune intervention and disease response. There is a propensity for extramedullary disease recurrence in patients whose marrow disease is controlled with immunologic manipulation. Exploration of GVM outside conventional allogeneic transplantation or after autologous transplantation is necessary to increase the number of patients likely to benefit from this phenomenon and to make it safer. This article reviews the currently available literature on the subject. [ABSTRACT FROM AUTHOR]

Forty-two patients allografted for multiple myeloma after not having attained at least a partial remission (n = 19) or after having experienced disease progression (n = 23) following one autograft were compared with 42 pair-matched controls who underwent salvage autotransplantation under identical conditions. Autografted controls were matched closely for albumin, C-reactive protein, creatinine, disease sensitivity, duration of standard therapy prior to the first transplant, Ig isotype, karyotype, LDH, and response to the first transplant, but, in comparison to allografted patients, were older, had higher Β2-microglobulin, and had a shorter interval between the two transplants. The complete remission rate was 41% after allogeneic and 33% after autologous transplantation (P = NS). The 3-year probability of event-free survival was comparable for the two groups (25 ± 8% after autografting and 20 ± 8% after allografting). The 3-year probability of survival was significantly higher after autologous transplantation (54 ± 8% vs 29 ± 9%; P = 0.01). Twenty-one patients in the autograft group were alive 11-59 months (median 32) following the second transplant, while 15 patients in the allograft group were alive at 10-53 months (median 20). The 3-year probability of disease progression was significantly lower after allogeneic transplantation (31 ± 10% vs 72 ± 9%, P = 0.03). The 1-year probability of transplant-related mortality was significantly higher after allografting (43 ± 8% vs 10 ± 5%; P= 0.0001). We conclude that while autografting appears to be superior to allografting for salvage therapy of myeloma persisting or relapsing after one previous autotransplant in terms of overall survival, event-free... [ABSTRACT FROM AUTHOR]

Eighteen extensively pre-treated patients (35–73 years, median 46) with relapsed multiple myeloma received salvage chemotherapy with 6 g/m2 cyclophosphamide, 800 mg/m2 carboplatin, and 1800 mg/m2 etoposide (CCV) as a 96-h continuous infusion followed by autologous peripheral blood stem cells. The median number of prior chemotherapy regimens was five (range 4–10), including at least one autograft. Four patients died of toxicity, and one developed dialysis-dependent renal failure, while the others tolerated CCV well. Three of six patients with pre-transplant creatinine of >1 mg/dl died of toxicity compared with one of 12 with creatinine 1 mg/dl (P = 0.083, Fisher’s exact test). Three of four patients treated with four previous regimens showed >50% reduction in tumor compared with one of 14 treated with >4 regimens (P = 0.02, Fisher’s exact test). At the last follow-up, five patients were alive at 8–24 months (median 13) with stable (n = 1) or progressive (n = 4) disease, and nine had died of progressive disease at 2.5–15 months (median 7). We conclude that CCV chemotherapy with autografting is tolerated well by extensively pre-treated myeloma patients provided the pre-transplant creatinine is normal, but toxicity in patients with abnormal renal function is high. The efficacy in multiply relapsed disease is poor, with response in only 22% of patients. CCV may deserve further evaluation early in the course of myeloma in patients with normal renal function. [ABSTRACT FROM AUTHOR]