Abstract
Background
Treatment with high-dose chemotherapy and stem cell transplantation has prolonged survival in patients of multiple myeloma (MM). A dose-response relationship between number of CD34+ cells infused and leukocyte and platelet recovery, exists. Patients receiving dose of <2.0 × 106 CD34+ cells/kg have delayed engraftment. The level of optimal cutoff for accelerated engraftment is yet to be validated. Hence, this study was undertaken to study the association of CD 34+ cell dose with engraftment kinetics in patients of MM who underwent autolgous peripheral blood stem cell transplant (PBSCT).
Methods
We retrospectively analyzed 19 patients of MM who underwent PBSCT at our center between December 2016 to December 2018. Complete blood counts were carried out daily after transplantation to record neutrophil and platelet engraftment.
Results
Based on the CD34+ cell dose given : <5 × 106/kg (category 1), 5−10 × 106/kg (category 2), >5 × 106/kg (category 3), the mean (SD) neutrophil engraftment time was 11.3 (0.5) days, 10.6 (0.9) days, and 10.2 (1.3) days respectively. Platelet engraftment time was 12.4 (2.60) days, 10.6 (1.14) days, and 11.2 (1.64) days for category 1, 2, and 3 patients, respectively. Correlation co-efficient between CD 34+cell dose and days for neutrophil and platelet engraftment was found to be −0.24 and −0.20, respectively. Time for neutrophil engraftment was found to be significantly associated with CD34+ cell dose category.
Conclusion
CD 34+ cell dose appears as the strongest predictor of leukocyte and platelet engraftment. CD 34+ cell dose of >5.0 × 106 cells/kg leads to an accelerated neutrophil and platelet engraftment in patients of MM.
Keywords: CD 34 cell dose, Engraftment, PBSCT, Multiple myeloma, Plerixafor
Introduction
Multiple myeloma (MM) is a hematological malignancy with an accumulation of plasma cells in the bone marrow along with the presence of monoclonal proteins in serum and/or urine.1,2
Over the last two decades, Stem Cell Transplant (SCT) has gradually replaced chemotherapy as the preferred treatment in eligible MM patients, as comparative complete remission rates, event-free survival (EFS), and overall survival (OS) is better post-SCT.3, 4, 5, 6 Concurrent use of novel agents such as immunomodulatory drugs, monoclonal antibodies, and proteasome inhibitors has reinforced the pivotal role of SCT as the standard of care in MM while enhancing survival proportionately.7,8
For patients on therapy, recommended induction therapy consists of a three-drug regimen followed by the collection of hematopoietic stem cells. For patients eligible to undergo SCT, high dose melphalan followed by autologous stem cell transplant (ASCT) remains the standard regimen,8 as it helps in increasing both the frequency and grade of responses leading to improved outcomes. Allogenic SCT is also curative, but it entails higher rates of procedure-related mortality and relapse. Moreover, patients frequently relapse after the procedure.
The minimum dose of CD 34+ cells/kg promulgated for adequate engraftment in Peripheral Blood Stem Cell Transplantation (PBSCT) is 2 × 106 CD 34+ cells/kg of the recipient; however, engraftment is expedited with higher CD 34+ cell doses.9 A dose–response relationship between CD 34+ cells infused and neutrophil and platelet engraftment exists.10,11
In patients treated with myeloid growth factors after PBSCT, PBSC products with CD 34+ cell doses >10 × 106/kg body weight of recipient lead to swifter hematopoietic recovery than the infusion of 5–10 × 106 CD 34 cells/kg.7 Further, patients infused with <2 × 106 CD 34+ cells/kg have a significantly delayed platelet recovery as compared to those getting PBSC products with a higher CD 34+ cell dose.9,11 Other factors that influence hematopoietic recovery include age at disease onset, duration of prior therapy, the extent of prior treatment with alkylating agents, and source of transplant.12
While there is a consensus regarding the minimum CD 34+ cell dose required for adequate engraftment (2 × 106/kg), the level of optimal cut off for accelerated engraftment is yet to be elucidated and validated. Hence, this study was undertaken to study the association of CD 34+ cell dose with engraftment kinetics in autologous PBSCT patients of MM.
Materials and methods
To evaluate the effect of CD 34+ cell dose on hematopoietic engraftment, we retrospectively analyzed 19 patients of MM in our institution over a period of two years (Dec 2016 to Dec 2018).
A written informed consent was taken from all patients. The study was approved by the Institutional Ethics Committee.
Chemotherapy regime
Out of 19 patients, 9 patients were given chemotherapy in the form of VLD (Bortezomib-Lenalidomide-Dexamethasone), two were given VTD (Bortezomib-Thalidomide-Dexamethasone), while eight were given VCD (Bortezomib-Cyclophosphamide-Dexamethasone). None of the patients received radiotherapy.
Conditioning regimen
The preparative regimen consisted of Inj. Melphalan (140 mg/m2 or 200 mg/m2) IV infusion over 15 min. The majority of patients received conditioning with 200 mg/m2 melphalan, while dose reduction to 140 mg/m2 was required for six patients in the elderly group.
Mobilization and collection
Peripheral Blood Stem Cell (PBSC) mobilization was achieved using high-dose Cyclophosphamide and hematopoietic growth factors Inj Granulocyte-Colony Stimulating Factor (G-CSF 10 μg/kg/day). The marrow in patients of MM is diseased, making it a challenge to get an adequate stem cell yield in some patients. Hence three patients were also given Inj Plerixafor (0.24 mg/kg/dose) after poor mobilization by G-CSF alone, as assessed by peripheral blood CD 34+ cell counts of patients. PBSC harvests were done using a continuous flow cell separator system (ComTec, Fresenius-Kabi, Hamburg, Germany) on day four or five of Inj G-CSF initiation depending on the pre-procedure peripheral blood CD 34+ cell counts by flow cytometry. A cut-off of at-least 10 CD 34+ cells/μl was taken to initiate collection. A four-color BD FACS Calibur platform was used, and enumeration was done using the ISHAGE protocol.15 The PBSC products were grouped into three categories based on their CD 34+ cell counts: 2–5 × 106/Kg, 5–10 × 106/Kg, and >10 × 106/Kg.
Out of 19 MM patients, 13 patients underwent 1 apheresis procedure, four patients underwent two apheresis procedures, while one patient underwent four apheresis procedures. The duration of illness in this patient was more than 7 years, which may explain the poor response of bone marrow.
Engraftment and supportive care
Complete blood counts were done daily following SCT until complete engraftment was achieved. Engraftment was defined from the day of PBSC reinfusion (day 0) until absolute neutrophil counts (ANC) were stable at 500/mm3 for at least 3 days. The time to platelet engraftment was defined as the number of days taken for the platelet count to be stable over 20,000/mm3 for 3 consecutive days without any platelet transfusion. Platelets were prophylactically transfused in cases where thrombocytopenia was below 10,000/mm3. Red blood cell transfusions were given when the patients’ hemoglobin was <7 g/dL or when they had symptomatic anemia. All blood components were irradiated and leucodepleted. No patients received G-CSF after high dose chemotherapy (HDC) and transplantation. Patients were given a broad-spectrum antibiotic, antiviral, and antimycotic therapy as per standard operating procedures (SOPs) of the hospital.
Statistical analysis
Statistical analysis was done using R3.6.0 software. Data were summarized by calculating mean, median, range, standard deviation, and proportions. Patients were categorized as Category 1 if CD 34+ cell dose was less than 5 × 106/kg, Category 2 if it was between 5 × 106/kg −10 × 106/kg, and Category 3 if it was more than10 × 106/kg. Pearson’s correlation coefficient with 95% Confidence Intervals (CI) was calculated between the CD 34+ cell dose and time for neutrophil and platelet engraftment. Association of time taken neutrophil and platelet engraftment with various factors was assessed by linear regression analysis. Two-tailed tests were used, and a P value of <0.05 was considered to be statistically significant.
Results
Out of the total 19 study participants, 15 were males and 04 were females. The median age of patients was 57 years (range 41–69 years). Mean (SD) height, weight and body surface area (BSA) of study participants was 164.74 (6.09) cm, 64.37 (12.42) kg, and 1.69 (0.17) m2, respectively. The average duration of illness before SCT was done was 30 months (range 6 months–7 years). Table 1 summarises the baseline characteristics of study participants.
Table 1.
Baseline characteristics of patients included in the study (n = 19).
| Characteristics | No. of patients (%) |
|---|---|
| Gender | |
| Male | 15 (78.9) |
| Female | 04 (21.1) |
| Age (yrs) | |
| 41–50 | 04 (21.1) |
| 51–60 | 11 (57.8) |
| 61–70 | 04 (21.1) |
| Body Surface Area (kg/m2) | |
| 1.41–1.60 | 08 (42.1) |
| 1.61–1.80 | 06 (31.6) |
| 1.81–2.00 | 05 (26.3) |
| Mean duration of illness prior to transplant | |
| <1 yr | 09 (47.4) |
| 1–5 yr | 07 (36.8) |
| >5 yr | 03 (15.8) |
| Chemotherapy regime | |
| Bortezomib-Lenalidomide-Dexamethasone (VLD) | 09 (47.4) |
| Bortezomib-Thalidomide-Dexamethasone (VTD) | 02 (10.5) |
| Bortezomib-Cyclophosphamide-Dexamethasone (VCD) | 08 (42.1) |
| Mobilization regime | |
| Inj G-CSF | 16 (84.2) |
| Inj G-CSF + Plerixafor | 03 (15.8) |
| Conditioning regime | |
| Inj Melphalan 140 mg/m2 | 06 (31.6) |
| Inj Melphalan 200 mg/m2 | 13 (68.4) |
Mean (SD) postprocedure CD 34+ cell dose was 7.27 (5.60) × 106/kg while mean preprocedure CD 34+ cell count was 37.16(21.24)/μL. Mean (SD) days for engraftment of neutrophil and platelets were 10.83 (0.95) days and 11.62 (2.13) days, respectively. Nine study participants were given CD 34+ cell dose less than 5 × 106/kg (Category 1), and their mean (SD) neutrophil engraftment time was 11.3 (0.5) days, while it was 10.6 (0.9) days and 10.2 (1.3) days, respectively, for Category 2 (five patients) and Category 3 (five patients) study participants (Fig. 1). Platelet engraftment time was 12.4 (2.60) days, 10.6 (1.14) days and 11.2 (1.64) days for patients of Category 1, 2, and 3, respectively (Fig. 2).
Fig. 1.
Days for Neutrophil engraftment in patients with different cell dose category (Category 1 - CD 34+ cell dose < 5 × 106/kg, Category 2 - CD 34+ cell dose between 5 × 106/kg - 10 × 106/kg Category 3 - CD 34+ cell dose > than10 × 106/kg.).
Fig. 2.
Days for Platelet engraftment in patients with different cell dose category. (Category 1 - CD 34+ cell dose < 5 × 106/kg, Category 2 - CD 34+ cell dose between 5 × 106/kg - 10 × 106/kg, Category 3 - CD 34+ cell dose > than10 × 106/kg.)
Correlation coefficient between CD 34+ cell dose and days for neutrophil and platelet engraftment was found to be −0.24 (95% CI: −0.63, 0.24, p = 0.319) and –0.20 (95% CI: −0.60, 0.28, p = 0.402) respectively. Correlation coefficient between days for neutrophil and platelet engraftment was 0.27 (95% CI: –0.21, 0.64, p = 0.267).
Time for neutrophil engraftment was found to be significantly associated with CD 34+ cell dose category (β = –0.58 (95% CI: –1.07, –0.09), p = 0.023) and number of apheresis cycles (β = 1.03(95% CI: 0.08, 1.98), p = 0.035) (Table 2). However, no significant association was found between neutrophil engraftment and age, sex, height, weight, BMI, body surface area, duration of illness, conditioning regimen, or pre CD 34 levels of the patients. Similarly, no significant association was observed between platelet engraftment and other variables (Table 2).
Table 2.
Factors associated with neutrophil and platelet engraftment.
| Neutrophil engraftment |
Platelet engraftment |
|||
|---|---|---|---|---|
| Regression coefficient (95% CI) | P value | Regression coefficient (95% CI) | P value | |
| Cell dose category | –0.58 (–1.07, –0.09) | 0.023 | 0.720 (–1.95, 0.51) | 0.232 |
| Apheresis | ||||
| 1 cycle >1 cycle |
Ref 1.03 (0.08, 1.98) |
0.035 | Ref 1.59 (–0.69, 3.87) |
0.161 |
The common toxicities were mucosal ulcerations and infections. The day-100 post ASCT treatment-related mortality (TRM) was nil.
Discussion
Our study analyzed the effect of CD 34+ cell dose along with other patient dependent factors affecting engraftment kinetics in autologous PBSCT patients of MM.
Our study had a male preponderance that has generally been seen in most studies.16,17 Ninety-eight percent of cases of myeloma are clustered over the age of 40 years, with a peak incidence between 65 and 70 years.1 These findings are also reflected in our study (Table 1). Many experts consider age as an important parameter while deciding the suitability for proceeding to high-dose therapy (HDT) followed by ASCT with a cut-off of 65 years being widely used in clinical trials for patient enrolment.2 In our study, the median age of patients undergoing transplant was 57 years. However, age, gender, and body mass index did not have any effect on engraftment kinetics.12,18
Patients are generally mobilized using G-CSF and chemotherapy, typically high dose melphalan prior to PBSC collection.9 Garderet et al reported improved survival rates in ASCT patients more than 65 years old when melphalan was administered at a dose of 200 mg/m2 compared to 140 mg/m2 and induction was Bortezomib-based. No treatment-related mortality was reported.19 Further, various studies and meta-analyses have stated the advantage of using VTD (Bortezomib-Thalidomide-Dexamethasone) or VLD (Bortezomib-Lenalidomide-Dexamethasone) as induction therapy over VCD (Bortezomib-Cyclophosphamide-Dexamethasone).13,14 Our study showed no significant association between the type of chemotherapy regimen used and engraftment.
Our study showed a positive association between a higher dose of transfused autologous stem cells and outcome, as shown in earlier studies.20, 21, 22,20, 21, 22,20, 21, 22 Kiss et al reported the existence of a threshold effect between rapid and slow engraftment at CD 34+ cell dose cut off of 5 × 106 CD 34+ cells/kg.23 Other studies have also found a dose-effect relationship for platelets up to doses of 10 × 106 CD 34+ cells/kg.24,25 Our study corroborates results of previous studies suggesting that an increasing number of transplanted stem cells improve hematopoietic engraftment of patients after high-dose therapy.10,11 Analysis of transplant data of our 19 patients of MM revealed that a CD 34+ cell dose of ≥5 × 106 cells/kg leads to accelerated engraftment. The minimum cell dose given in our study was 2.53 × 106 CD 34+ cells/kg. All patients had neutrophil engraftment by 12 days and platelet engraftment by 19 days. For enhancing the chances of engraftment, a threshold CD 34+ cell dose of 2.5 × 106/kg in PBSCT is currently used at our institution.
While CD 34+ cell dose emerges as the most robust predictor of engraftment, pretransplant factors also play a significant role. It has been shown that greater the length of previous treatments and more number of chemotherapy regimens are associated with delayed leucocyte and platelet engraftment. Tricot et al showed that a minimum CD 34+ cell dose of 5 × 106/kg was necessary for rapid platelet recovery in heavily pretreated patients of MM.26Our patients showed adequate engraftment with a minimum threshold of 2.5 × 106 CD 34+ cells/kg in a PBSCT, irrespective of the length of previous therapy or treatment with alkylating agents.
Our study also confirmed the study done by Haas et al, which showed a significant impact of CD 34+ cell dose on long-term platelet engraftment in MM patients.27
In our study, CD 34+ cell dose emerged as the only important parameter, after multivariate analysis, which significantly determined leucocyte or platelet reconstitution. Although our study is limited by its small sample size(n = 19), the trend of engraftment kinetics favors a higher CD 34 cell dose (>5 × 106/Kg) for better engraftment and outcomes.
Our study found that higher CD 34+ cell dose (cut-off > 5 × 106/Kg) in PBSCT correlated with faster hematopoietic engraftment, and hence, ensured better patient outcome, decreased hospital stay, and reduced cost of transfusion support post-transplant. Larger multicentric studies in Indian scenarios are required to study the effects of other patient parameters on engraftment, overall survival, and disease-free survival in patients of MM.
Disclosure of competing interest
The authors have none to declare.
References
- 1.Hoffbrand A.V., Moss P.A.H. 7th ed. Wiley Blackwell; 2016. Hoffbrand's Essential Haematology. [Google Scholar]
- 2.Ntanasis-Stathopoulos I., Gavriatopoulou M., Kastritis E., Terpos E., Dimopoulos M.A. Multiple myeloma: role of autologous transplantation. Canc Treat Rev. 2020 Jan;82:101929. doi: 10.1016/j.ctrv.2019.101929. [DOI] [PubMed] [Google Scholar]
- 3.Gay F., Oliva S., Petrucci M.T., et al. Chemotherapy plus lenalidomide versus autologous transplantation, followed by lenalidomide plus prednisone versus lenalidomide maintenance, in patients with multiple myeloma: a randomised, multicentre, phase 3 trial. Lancet Oncol. 2015;16(16):1617–1629. doi: 10.1016/S1470-2045(15)00389-7. [DOI] [PubMed] [Google Scholar]
- 4.Gertz M.A., Dingli D. How we manage autologous stem cell transplantation for patients with multiple myeloma. Blood. 2014;124(6):882–890. doi: 10.1182/blood-2014-03-544759. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Blade J. Controversy in hematology Transplantation for multiple myeloma : who , when , how often ? High-dose therapy in multiple myeloma. Blood. 2003;102(10):3469–3477. doi: 10.1182/blood-2003-01-0073. [DOI] [PubMed] [Google Scholar]
- 6.Al Hamed R., Bazarbachi A.H., Malard F., Harousseau J.L., Mohty M. Current status of autologous stem cell transplantation for multiple myeloma. Blood Canc J. 2019;9(4):44. doi: 10.1038/s41408-019-0205-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Costa L.J., Zhang M.J., Zhong X., et al. Trends in utilization and outcomes of autologous transplantation as early therapy for multiple myeloma. Biol Blood Marrow Transplant. 2013;19(11):1615–1624. doi: 10.1016/j.bbmt.2013.08.002. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.McCarthy P.L., Hahn T., Hassebroek A., et al. Trends in use of and survival after autologous hematopoietic cell transplantation in north America, 1995-2005: significant improvement in survival for lymphoma and myeloma during a period of increasing recipient age. Biol Blood Marrow Transplant. 2013;19(7):1116–1123. doi: 10.1016/j.bbmt.2013.04.027. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Arora S., Majhail N.S., Liu H. Hematopoietic progenitor cell mobilization for autologous stem cell transplantation in multiple myeloma in contemporary era. Clin Lymphoma, Myeloma & Leukemia. 2019 Apr;19(4):200–205. doi: 10.1016/j.clml.2018.12.010. [DOI] [PubMed] [Google Scholar]
- 10.Nath K., Boles R., McCutchan A., Vangaveti V., Birchley A., Irving I. The relationship between CD34+ stem cell dose and time to neutrophil recovery in autologous haematopoietic stem cell recipients-A single centre experience. Transfus Apher Sci. 2018 Aug;57(4):532–536. doi: 10.1016/j.transci.2018.05.031. [DOI] [PubMed] [Google Scholar]
- 11.Martin R.M.G., Ricci M.J., Foley R., Mian H.S. The relationship of CD34+ dosage and platelet recovery following high dose chemotherapy and autologous CD34+ reinfusion in multiple myeloma. Transfus Apher Sci. 2017;56(4):552–557. doi: 10.1016/j.transci.2017.06.002. [DOI] [PubMed] [Google Scholar]
- 12.Hassan M.N., Fauzi H.M., Husin A., et al. Autologous peripheral blood stem cell transplantation among lymphoproliferative disease patients: factors influencing engraftment. Oman Med J. 2019 Jan;34(1):34–43. doi: 10.5001/omj.2019.06. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Leiba M., Kedmi M., Duek A., et al. Bortezomib-Cyclophosphamide-Dexamethasone (VCD) versus Bortezomib-Thalidomide-Dexamethasone (VTD) -based regimens as induction therapies in newly diagnosed transplant eligible patients with multiple myeloma: a meta-analysis. Br J Haematol. 2014 Sep 1;166(5):702–710. doi: 10.1111/bjh.12946. [DOI] [PubMed] [Google Scholar]
- 14.Moreau P., Hulin C., Macro M., et al. VTD is superior to VCD prior to intensive therapy in multiple myeloma: results of the prospective IFM2013-04 trial. Blood. 2016 May 26;127(21):2569–2574. doi: 10.1182/blood-2016-01-693580. [DOI] [PubMed] [Google Scholar]
- 15.Sutherland D.R., Anderson L., Keeney M., Nayyar R., Chin-Yee I. The ISHAGE guidelines for CD34+ cell determination by Flow cytometry. J Hematother. 1996 Jan 1;5:213–226. doi: 10.1089/scd.1.1996.5.213. [DOI] [PubMed] [Google Scholar]
- 16.Kumar L., Ramavath D., Kataria B., et al. High-dose chemotherapy followed by autologous stem cell transplant for multiple myeloma: predictors of long-term outcome. Indian J Med Res. 2019 Jun;149(6):730–739. doi: 10.4103/ijmr.IJMR_1593_18. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Posch D., Rabitsch W., Wohlfarth P., et al. Gender-specific aspects in patients with multiple myeloma undergoing autologous stem cell transplantation: a single-center experience. Oncology. 2017;93(5):295–301. doi: 10.1159/000478265. [DOI] [PubMed] [Google Scholar]
- 18.Khouri J., Rybicki L., Majhail N.S., et al. Body mass index does not impact hematopoietic progenitor cell mobilization for autologous hematopoietic cell transplantation. J Clin Apher. 2019;(February):1–8. doi: 10.1002/jca.21739. [DOI] [PubMed] [Google Scholar]
- 19.Garderet L., Beohou E., Caillot D., et al. Upfront autologous stem cell transplantation for newly diagnosed elderly multiple myeloma patients: a prospective multicenter study. Haematologica. 2016 Nov 1;101(11):1390–1397. doi: 10.3324/haematol.2016.150334. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Stiff P.J., Micallef I., Nademanee A.P., et al. Transplanted CD34+ cell dose is associated with long-term platelet count recovery following autologous peripheral blood stem cell transplant in patients with non-hodgkin lymphoma or multiple myeloma. Biol Blood Marrow Transplant. 2011 Aug 1;17(8):1146–1153. doi: 10.1016/j.bbmt.2010.11.021. [DOI] [PubMed] [Google Scholar]
- 21.Nagayama T., Ashizawa M., Ikeda T., et al. Factors that predict delayed platelet recovery after autologous stem cell transplantation for lymphoma or myeloma. Ann Hematol. 2020 doi: 10.1007/s00277-020-04112-4. Available from: [DOI] [PubMed] [Google Scholar]
- 22.Aladağ Karakulak E., Demiroğlu H., Büyükaşik Y., et al. CD34+ Hematopoietic progenitor cell dose as a predictor of engraftment and survival in multiple myeloma patients undergoing autologous stem cell transplantation. Turkish J Med Sci. 2020 Jun doi: 10.3906/sag-2001-173. [Internet]. Available from: [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Kiss J.E., Rybka W.B., Winkelstein A., et al. Relationship of CD34+ cell dose to early and late hematopoiesis following autologous peripheral blood stem cell transplantation. Bone Marrow Transplant. 1997;19(4):303–310. doi: 10.1038/sj.bmt.1700671. [DOI] [PubMed] [Google Scholar]
- 24.Remes K., Matinlauri I., Grenman S., et al. Daily measurements of blood CD34+ cells after stem cell mobilization predict stem cell yield and posttransplant hematopoietic recovery. J Hematother Stem Cell Res. 1997;6(1):13–19. doi: 10.1089/scd.1.1997.6.13. [DOI] [PubMed] [Google Scholar]
- 25.Goldschmidt H., Hegenbart U., Wallmeier M., et al. High-dose therapy with peripheral blood progenitor cell transplantation in multiple myeloma. Ann Oncol. 1997;8(3):243–246. doi: 10.1023/a:1008252227512. [DOI] [PubMed] [Google Scholar]
- 26.Tricot G., Jagannath S., Vesole D., et al. Peripheral blood stem cell transplants for multiple myeloma: identification of favorable variables for rapid engraftment in 225 patients. Blood. 1995;85(2):588–596. [PubMed] [Google Scholar]
- 27.Haas R., Witt B., Mohle R., et al. Sustained long-term hematopoiesis after myeloablative therapy with peripheral blood progenitor cell support. Blood. 1995;85(12):3754–3761. [PubMed] [Google Scholar]