Bone marrow transplant method and apparatus

A bone marrow transplant method and apparatus has been devised for the efficient recovery of bone marrow from a donor or patient by inserting a pair of aspiration needles at the intended site of removal and, through connection with a pair of syringes, the pressure is regulated to bring about selective removal of bone marrow and sinusoidal blood through one of the aspiration needles while positively forcing an intravenous solution through the other of the aspiration needles to replace the bone marrow removed from the site. The bone marrow and sinusoidal blood are drawn into a chamber for mixture with another intravenous solution and thereafter forced into a collection bag. A disposable assembly is provided for ready interchangeable use in association with a fluid flow and valve control unit in carrying out the method and principles of the present invention.

This invention relates to a novel and improved method and apparatus 
adaptable for use in medical transplant procedures; and more particularly 
to a method and apparatus for efficiently recovering bone marrow in bone 
marrow transplant operations. 
BACKGROUND AND FIELD OF THE INVENTION 
In the past, bone marrow transplants have been performed with success but 
have involved considerable pain due mainly to the number of bone marrow 
aspirations which must be performed. Bone marrow is comprised of bone 
marrow cells and large volumes of sinusoidal blood. For instance, it is 
not uncommon to have to insert a needle on the order of fifteen to seventy 
times into different sites or locations in order to recover acceptable 
quantities of bone marrow. Moreover, the bone marrow which is extracted is 
not separated from the sinusoidal blood, and in transfusing substantial 
volumes of material into the recipient, the bone marrow cavity is so 
finite and limited in capacity that it cannot readily accommodate huge 
volumes of blood and bone marrow. Thus, it is customary to inject the mass 
of material into the vein and depend upon the bone marrow present to find 
its way back into the marrow of the patient so as to function as normal 
marrow and undergo normal growth. A typical case requiring bone marrow 
transplantation is one in which healthy bone marrow is removed from a 
cancer patient prior to chemotherapy and the same bone marrow reinfused 
into the patient after chemotherapy. Another example is the need for bone 
marrow transplantation into a patient with decreased bone marror function 
as in aplastic anemia or bone marrow failure due to drugs. In this latter 
situation, healthy bone marrow must be removed from a healthy donor with 
the healthy marrow being infused into the recipient patient. 
It is therefore desirable to provide for a method and apparatus by means of 
which bone marrow may be harvested from a patient with a minimal number of 
needle placements which are capable of being performed under local 
anethesia over a relatively short period of time. Moreover, it is 
desirable that the procedure be virtually painless once the needles are 
inserted into the patient so as to avoid activation of stretch receptors 
in the marrow cavity. 
SUMMARY OF THE INVENTION 
It is therefore an object of the present invention to provide for a novel 
and improved method and apparatus for bone marrow transplants. 
It is another object of the present invention to provide for a novel and 
improved method of carrying out bone marrow transplant operations in which 
the bone marrow can be withdrawn from a single site and collected for 
injection into a patient and in such way as to eliminate stretching or 
activation of the nerve stretch receptors in the marrow cavity thereby 
virtually eliminating bore marrow aspiration pain. 
A further object of the present invention is to provide for a novel and 
improved bone marrow transplant apparatus including common actuating means 
to regulate the relative pressures in the various lines leading to and 
from a donor or patient. 
It is an additional object of the present invention to provide in a bone 
marrow apparatus for a disposable assembly removably connectable to the 
patient as well as to various sources of solution supply and collector for 
the purpose of carrying out bone marrow transplant procedures in a safe, 
rapid and relatively painless manner. 
In accordance with the present invention, a preferred form of bone marrow 
apparatus is capable of effecting removal of bone marrow and sinusoidal 
blood from a donor or patient at a single site, the material withdrawn 
from the patient being replaced by a suitable form of intravenous 
solution, such as, a mixture of an anticoagulant and saline or electrolyte 
solution. The bone marrow and sinusoidal blood removed from the patient 
are transferred either into a cell separator or suitable collection bag so 
as to permit separation of the bone marrow for subsequent processing or 
reinjection back into the same patient or into another patient. In the 
removal of the bone marrow from the patient or donor, an intravenous 
solution consisting of heparin or other anticoagulant compositions 
together with a saline solution are mixed with the bone marrow and 
sinusoidal blood preliminary to transfer into the separating or collecting 
means. 
These steps are accomplished in the present invention by a unique form of 
apparatus in which a series of lines are directed from a chamber section 
to a soruce of intravenous solution, an aspiration needle, a second source 
of intravenous solution and a suitable separating or collection source as 
described. The chamber section is characterized by being capable of 
simultaneously applying negative pressure to the solution lines leading 
from the intravenous solution sources in order to prime the lines and to 
purge them of any air. The solution lines are then closed and a positive 
pressure applied to redirect the intravenous solution into the donor while 
negative pressure is applied to withdraw the bone marrow material into a 
chamber for admixture with the intravenous solution, following which a 
positive pressure is applied to transfer the mixture of the intravenous 
solution and bone marrow material into the separating or collection 
source. A single chamber with a double-acting plunger may be employed in 
one form to carry out the steps of the present invention, but in the 
preferred form a dual chamber having separate plungers are arranged to be 
simultaneously controllable by a common actuator to establish the desired 
positive and negative pressures in the respective lines.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT 
Referring to FIGS. 5 and 6, a cabinet or base 10 is provided for mounting 
of a disposable assembly 12, the latter being illustrated in FIGS. 1 to 4. 
The cabinet 10 is broadly comprised of a relatively shallow, generally 
rectangular receptacle 14 preferably comprised of a transparent bottom 
panel 15 with a generally circular light tube or lamp 16 mounted beneath 
the panel. 
To one side of the receptacle are a pair of solenoid-operated control 
valves designated at V.sub.1 and V.sub.2 ; and to the opposite side of the 
receptacle are solenoid-operated control valves V.sub.3, V.sub.4 and 
V.sub.5. Each control valve is mounted in association with an elongated 
groove designated G.sub.1 to G.sub.5, respectively, and each groove 
extending from communication with a sidewall of the receptacle and 
extending in a longitudinal direction across the top surface 18 of a cover 
plate designated at 20 which is removably secured over the cabinet by 
means of suitable fasteners 21. In addition, the cabinet is designed to 
contain the necessary power source and controls for operation of the 
solenoids including transformer section 22, control panel 23 and circuit 
board section 24. Opposite end walls of the cabinet are provided with 
shallow recessed areas 26 which facilitate grasping of the unit or in 
other words serve as hand grips. 
From a consideration of FIGS. 5 and 6, it will be noted that the lower 
panel 15 of the receptacle is provided with a shallow groove 30 which 
extends intermediately across the length of the receptacle and in a 
direction transversely to the length of the entire cabinet. The groove is 
provided with dovetailed sides 31 to permit retention and slidable 
insertion of an actuator assembly 32, the actuator including a lower flat 
plate 34 of oblong configuration adapted to traverse the entire length of 
the groove 30 and having upstanding, plunger-engaging brackets 35 and 35'. 
The bracket 35 is located just less than halfway along the length of the 
slide 34, and the bracket 35' is located in offset relation to bracket 35 
and at a position adjacent to the distal end of the slide 34. Each bracket 
comprises closely-spaced parallel wall sections including a generally 
channel-shaped wall section 36 and 36', respectively, and a solid wall 
section 37 and 37', respectively, with a narrow recess 38 and 38', 
respectively, formed between the wall sections, all for a purpose to be 
described. In addition, each bracket is aligned with a slot 39 and 39', 
respectively, each slot being of narrow elongated configuration and being 
formed through the thickness of the slide member in longitudinally 
centered relation to the bracket to serve as a seating portion for a 
syringe to be hereinafter described and to permit back lighting of the 
syringe body. In addition, the slide has a forwardly projecting hand grip 
40 at one end projecting from the sidewall of the receptacle with finger 
openings 41 to facilitate grasping and hand actuation or slidable movement 
of the entire actuator assembly 32. Located immediately below the 
receptacle portion of the cabinet is a relatively large cavity 42 for 
placement of ballast. 
FIGS. 1 to 4 illustrate the preferred form of disposable, fluid flow 
control assembly 12 which is broadly comprised of a relatively shallow 
tray having a bottom panel 50, side panels 52 and upstanding end panels 
53. Generally, the tray 12 is sized to be insertable into the receptacle 
14 with the end panels 53 aligned with opposite ends of the receptacle and 
with the top of the sides of panels 52, 53 of the tray flush with the 
upper surface of the receptacle. Upstanding locator blocks designated at 
54 are provided at spaced locations within the tray, each having a series 
of three upstanding locator pins 55 to serve as a means of location and 
support for fluid flow delivery lines to be described. Bosses 56 are 
positioned at spaced intervals around the periphery of the tray and at the 
center of the tray to threadedly receive the fastener screws 21 which 
extend through aligned bores in cover plate 20 of the cabinet. Also, 
locator pins 58 project upwardly from the bottom panel 50 of the tray to 
facilitate the location and mounting of a pair of chambers or syringes 60 
and 61 in horizontally extending, parallel but oppositely facing relation 
in a direction lengthwise of the tray and at a location aligned over the 
hand actuator assembly 32 in the receptacle. Each syringe may be of 
conventional construction and for example may be a Becton-Dickinson 
"Monoject" 20 cc. syringe having, as shown for syringe 61, an outer 
elongated cylindrical chamber section 62 terminating in a forward tapered 
end 63 which merges into a tube 64, and a flange 65 is disposed at its 
opposite end. As also shown for syringe 61, a plunger 66 is mounted for 
slidable movement through chamber section 62 and suitably provided with a 
piston head 67, a generally elongated shank 68 of X-shaped cross-section 
and handle or flange 69 at its external or trailing end. Syringe 60 is 
identical. Each chamber section 62 of a syringe is seated in the tray such 
that the tapered end abuts a pair of spaced locator pins 58 and the flange 
65 is snugly positioned between spaced pairs of locator pins 58 as 
illustrated. Immediately behind the locator pins 58 for each flange 65 is 
an elongated cavity 70 which extends through the thickness of the bottom 
panel 50 of the tray in alignment with the upstanding brackets 35 and 35', 
respectively, of the hand actuator assembly 32. The flanged end 69 of each 
plunger 66 is inserted into the groove 38 or 38' of a respective bracket 
with the channel-shaped wall section 36 or 36' flanking opposite sides of 
the plunger portion 68 and the solid wall portion of the bracket 38 or 38' 
located on the external side of the flanged end 69. Thus in the 
relationship shown in FIG. 5, the syringe 60 would have its plunger 66 
extended to a position such that the flanged end 69 would be aligned with 
the bracket 35' in the position illustrated in FIG. 5 while the syringe 61 
would have its flanged end 69 in the retracted position for alignment with 
the bracket 35. In response to sliding movement of the hand actuator 
assembly 32 outwardly, i.e., in a direction advancing downwardly as viewed 
in FIG. 5, the plunger 66 for syringe 61 is extended in following the 
movement of bracket 35 while the plunger 66 for syringe 61 is retracted. 
In other words, negative pressure would be created ahead of the plunger 66 
in the syringe 61 while positive pressure would be applied or created 
ahead of the plunger in the syringe 60 to force fluid in that chamber 
through the tube 64. 
As best seen from a consideration of FIGS. 3 and 4, the generally 
web-shaped or X-shaped cross-section of the plunger portions 68 are each 
supported on a generally V-shaped pin 74 which projects upwardly from the 
tray 50 adjacent to and at one end of each of the cavities 70. The support 
pins 74 operate to prevent accidental rotation of the plunger elements 66 
as they are extended and retracted with respect to their chambers 62. 
A series of delivery lines in the form of flexible conduits, such as, 
plastic tubing extend from the chambers 60 and 61 in such a manner as to 
be aligned with the grooves G.sub.1 to G.sub.5, as previously described 
with reference to FIGS. 5 and 6, and the external ends of the delivery 
lines which are directed away from opposite side panels 52 of the tray are 
designated L.sub.1 to L.sub.5, respectively. It will be noted that 
delivery lines L.sub.1 and L.sub.2 are joined at a tubular Y junction 75 
to a common line 76 which in turn is joined at a Y junction 78 to delivery 
line L.sub.3. Each of the Y junctions 75 and 78 are supported on a block 
54 between the locator pins 55 and the common line 76 from lines L.sub.1 
and L.sub.2 together with the line L.sub.3 is joined to the Y junction 78 
to line 80 which is connected by a suitable fitting or sleeve 82 to the 
tube 64 of chamber 61. Delivery lines L.sub.4 and L.sub.5 are joined 
through Y junction 84 to common line 86 which is secured by a fitting 88 
to the tube 64 of the chamber 60. Proper alignment of the delivery lines 
L.sub.1 to L.sub.5 in relation to the respective grooves G.sub.1 to 
G.sub.5 on the upper surface of the cabinet is established by a plurality 
of locator ribs 90 which are located at spaced intervals around the 
periphery of the tray. Intermediate ribs 92 project upwardly from the 
bottom panel 52 of the tray to assist in guiding the delivery lines 
between the tubes 64 and periphery of the tray. When the fluid flow 
control assembly 12 is positioned in the receptacle 14, as illustrated in 
FIG. 5, the delivery lines L.sub.1 and L.sub.2 are aligned with the 
grooves G.sub.1 and G.sub.2, respectively along one side of the 
receptacle. Delivery lines L.sub.3 to L.sub.5 are aligned with grooves 
G.sub.3 to G.sub.5, respectively on the opposite side of the receptacle. 
Referring to FIG. 5, it will be noted that a solenoid-operated control 
valve V is positioned beneath each of the grooves G, the valves being 
designated V.sub.1 to V.sub.5 for each of the respective grooves G.sub.1 
to G.sub.5 and associated delivery lines L.sub.1 to L.sub.5. Specifically, 
the delivery lines L are positioned in the manner shown in FIG. 6 such 
that they are fully inserted into their respective grooves G and are held 
in position by the cover plate 20. Each of the solenoid control valves V 
is correspondingly made up of a plunger or armature 94 which projects 
horizontally from one end of a solenoid 95, and each plunger 94 carries a 
movable valve element in the form of a pin 96 which projects upwardly from 
the plunger through a transverse slot 97 in the cover plate 20 at the 
leading end of each solenoid 95, there being a slot 97 (identified for 
V.sub.3 only) which intersects each one of the grooves G.sub.1 to G.sub.5. 
A mounting block 98 is mounted with its upper surface 100 directly beneath 
one of the associated grooves G.sub.1 to G.sub.5 with the movable pin 96 
and a stationary upwardly projecting pin 102 on the mounting block 
inserted in the slot 97 on opposite sides of the groove G. When the 
solenoid is de-energized, the plunger will normally be extended, as 
illustrated at valve location V.sub.3 with the movable pin 96 flanking one 
side of the groove G and the stationary pin 102 flanking the opposite 
side. When the solenoid is energized, it will cause retraction of the 
plunger and sliding movement of the pin 96 through the slot 97 into 
engagement with the delivery line L disposed in the groove G so as to 
pinch off or close the line as illustrated at solenoid V.sub.5. 
Accordingly, each solenoid is independently controllable to open or close 
its associated delivery line in regulating the flow of material through 
that line. 
In carrying out bone marrow transplant operations, in accordance with the 
present invention, the delivery line L.sub.1 extends from the associated 
groove G.sub.1 for connection to an intravenous drip chamber designated at 
106. Line L.sub.2 extends from groove G.sub.2 for connector 107 for a 
collection bag (not shown), such as, a collection bag manufactured and 
sold by Travenol Labs of Deerfield, Ill., under Code No. 4R6308. Line 
L.sub.3 extends from its groove G.sub.3 for connection to a Luer Lock 
fitting 108. Similarly, line L.sub.4 is connected to a Luer Lock fitting 
109, and finally line L.sub.5 is connected to a second intravenous drip 
chamber 110. In a well-known manner, the Luer Lock fittings facilitate 
releasable connection of aspiration and infusion needles placed in the 
patient. Preferably, the intravenous drip chamber 106 contains a saline or 
electrolyte solution having a predetermined concentration of heparin on 
the order of 4 units heparin per cubic centimeter for mixture with bone 
marrow and sinusoidal blood recovered from the patient through line 
L.sub.3. Similarly, the drip chamber 110 contains a saline or electrolyte 
solution with predetermined concentrations of heparin, on the order of 4 
units/cc. which is injected into the patient through line 109. In carrying 
out a bone marrow transplant, the various delivery lines should be primed 
or purged of any air so as to be completely filled with fluid as a 
preliminary to recovery or removal of bone marrow. Referring to the 
control panel and control buttons shown in FIG. 7, this is carried out by 
depressing "PRIME 1" to open valves V.sub.1 and V.sub.4 and close valves 
V.sub.2, V.sub.3, and V.sub.5, then depressing "PRIME 2" to reverse the 
position of the valves to open V.sub.2, V.sub.3 and V.sub.5 while closing 
V.sub.1 and V.sub.4, at the same time operating the hand actuator assembly 
32 until the tubes are filled with the intravenous solution drip chamber 
106, 107 the procedure being repeated until no bubbles appear in any of 
the lines. As a next step, "CLAMP" is depressed so that valves V.sub.1 and 
V.sub.5 are open and valves V.sub.2, V.sub.3 and V.sub.4 are closed so as 
to hold all output lines closed to eliminate leakage as a preliminary to 
insertion of the aspiration and infusion needles into the patient in the 
"CLAMP" position. Prior to attaching the Luer Locks 108 and 109 to the 
aspiration and infusion bone marrow needles, the bone marrow cavity is 
anti-coagulated with 2000 units of heparin. The needles connected to the 
Luer Locks 108 and 109 specifically are inserted into the same bone marrow 
site, such as as the iliac crest. As a next step, "PRIME ASPIRATE" is 
depressed to open the valves V.sub.1 and V.sub.5 open and close the 
remaining valves, then the hand actuator 32 is pulled out or withdrawn 
partially to permit the entry of the intravenous solution from drip 
chamber 106 prior to aspiration. At this point, "ASPIRATE" is depressed so 
that valves V.sub.3 and V.sub.4 are opened and valves V.sub.1, V.sub.2, 
and V.sub.5 are closed followed by fully withdrawing the hand actuator 
assembly in order to extract marrow from the patient. This is brought 
about by reason of the negative pressure created in the chamber 61 to 
induce the flow of bone marrow and sinusoidal blood into chamber 61. After 
the chamber 61 has been filled, "HARVEST" is depressed to open valves 
V.sub.2 and V.sub.5 and close valves V.sub.1, V.sub.3 and V.sub.4, 
following which the hand actuator is pushed in so as to retract the 
plunger 66 through chamber 61 and force the mixture of bone marrow, 
sinusoidal blood and intravenous solution through the line L.sub.2 which 
is connected to the collection bag spike 107. 
A modified form of chamber arrangement is shown in FIG. 8 which is 
adaptable for use in place of the double syringe assemblies 60, 61 of the 
preferred form. Specifically referring to FIG. 8, an outer cylinder 120 
includes a first port 121 at its leading end and a second port 122 in the 
sidewall adjacent to its rearward end. An O-ring seal 124 is positioned at 
the rearward end across the end surface of a closure 126 which is 
threadedly connected to the rear end of the cylinder 120. A central bore 
127 in the closure permits close-fitting slidable insertion of a plunger 
rod 128. Plunger rod 128 has an external handle 130 and a piston head 131 
which is arranged for slidable movement through the cylinder 120 in 
close-fitting sealed relation to its inner wall so as to in effect divide 
the inner space of the cylinder into a forward chamber 133 and a rear 
chamber 134. In this fashion, the forward chamber 133 is in communication 
with the end port 121 and the rearward chamber 134 is in communication 
with the rearward sidewall port 122. Reference is now made to FIG. 1 for 
an understanding of the manner in which the delivery lines would be 
connectable to the single, double-acting syringe: The delivery line 80 is 
connectable to the port 121 while the delivery line 86 is connectable to 
the sidewall port 122. Assuming that the double-acting syringe 120 is 
merely held in the hand, it will be appreciated that the system may be 
primed by successively opening and closing the same series of valves as 
described in connection with the preferred form as the plunger 128 is 
worked back and forth through the cylinder until the delivery lines are 
completely filled with intravenous solution and no bubbles appear. After 
holding all delivery lines closed through valves V.sub.2, V.sub.3 and 
V.sub.4 so as to eliminate any leakage, the aspiration needles are 
inserted into the patient, following which the plunger is withdrawn or 
advanced rearwardly through the cylinder 120 to allow entry of intravenous 
solution through the port 121 into chamber 133 prior to aspiration. Here 
the plunger is withdrawn only partially through the chamber, for example, 
to the position illustrated in FIG. 8, and thereafter is fully withdrawn 
rearwardly through the chamber 134 to extract bone marrow from the patient 
while maintaining valves V.sub.3 and V.sub.4 open and closing valves 
V.sub.1, V.sub.2 and V.sub.5. The mixture of bone marrow and intravenous 
solution is then ejected from the chamber 133 by advancing the plunger 
forwardly and forcing the mixture through delivery line 80 into the 
collection bag attached to the bag spike 107 while holding valves V.sub.2 
and V.sub.5 open and valves V.sub.1, V.sub.3 and V.sub.4 closed. 
The manner in which the valves V.sub.1 to V.sub.5 are controlled in opening 
and closing through the control panel is schematically represented in FIG. 
9. As shown in FIG. 9, a suitable power source represented at 140 is 
connected through transformer 142 and bridge circuit 143 to a heat sink 
144. In addition, the power supply is connected to the fluorescent lamp 
fixture 16 and through line 145 from the heat sink 144 to the valve 
control circuit generally designated at 150. In the valve control circuit, 
each of the buttons on the control panel as designated includes a manually 
depressable switch 152 which when depressed to a closed position serves to 
close the power supply into outlet lines leading to a gating circuit 
represented at 154 for each of the control lines into a respective valve. 
Each gating circuit from a control button has its output connected to a 
transistor circuit 155 which in turn leads into a solenoid circuit 156 for 
each respective valve. The sequence of opening and closing of the valves 
V.sub.1 to V.sub.5 is as previously described with the light displays 
which are designated at "1" through "5" as illustrated on the control 
panel in FIG. 7 being lit whenever an associated valve is closed. 
It will be appreciated from the foregoing that utilization of a disposable 
fluid flow control assembly which can be replaceably mounted in the main 
cabinet greatly facilitates reuse of the apparatus in performing bone 
marrow transplant operations. The versatility of the system is such that 
while it has been described specifically for use in connection with the 
recovery of bone marrow for transfer to a collection bag, it may as 
readily used for direct delivery into a cell separator unit. Thus, in the 
typical cases as previously described, it is possible to remove healthy 
bone marrow from a cancer patient prior to chemotherapy, then to reinfuse 
the same bone marrow into the patient after treatment. Alternately, where 
bone marrow is required for patients with decreased bone marrow functions, 
as in aplastic anemia or other bone marrow failure, healthy bone marrow 
may be efficiently and relatively painlessly removed from a healthy donor 
and infused into the recipient patient. 
It is therefore to be understood that various modifications and changes may 
be made in the specific sequence of steps as well as the construction and 
arrangement of parts in the preferred and modified forms of invention as 
described without departing from the spirit and scope of the present 
invention as defined by the appended claims.